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time-course transcriptome analysis of host cell response to poxvirus infection using a dual long-read sequencing approach.in this study, we applied two long-read sequencing (lrs) approaches, including single-molecule real-time and nanopore-based sequencing methods to investigate the time-lapse transcriptome patterns of host gene expression as a response to vaccinia virus infection. transcriptomes determined using short-read sequencing approaches are incomplete because these platforms are inefficient or fail to distinguish between polycistronic rnas, transcript isoforms, transcriptional start sites, as well as trans ...202134167576
development and characterization of a highly sensitive nanoluciferase-based immunoprecipitation system for the detection of anti-influenza virus ha antibodies.antibody detection is crucial for monitoring host immune responses to specific pathogen antigens (ags) and evaluating vaccine efficacies. the luciferase immunoprecipitation system (lips) was developed for sensitive detection of ag-specific antibodies in sera from various species. in this study, we describe nanolips, an improved lips assay based on nanoluciferase (nluc), and employ the assay for monitoring antibody responses following influenza virus infection or vaccination. we generated recombi ...202133980684
educational approach to prevent the burden of vaccinia virus infections in a bovine vaccinia endemic area in brazil.bovine vaccinia (bv), caused by vaccinia virus (vacv), is a zoonotic disease characterized by exanthematous lesions on the teats of dairy cows and the hands of milkers, and is an important public health issue in brazil and south america. bv also results in economic losses to the dairy industry, being a burden to the regions involved in milk production. in the past 20 years, much effort has been made to increase the knowledge regarding bv epidemiology, etiologic agents, and interactions with the ...202133922509
sars_cov2 rbd gene transcription cannot be driven by cmv promoter.cytomegalovirus (cmv) promoter drives various gene expression and yields sufficient protein for further functional investigation. receptor binding domain (rbd) on spike protein of the sars_cov2 is the most critical portal for virus infection. thus native conformational rbd protein may facilitate biochemical identification of rbd and provide valuable support of drug and vaccine design for curing covid-19. we attempted to express rbd under cmv promoter in vitro, but failed. rbd-specific mrna canno ...202133711560
genomic diversity of vaccinia virus strain cantagalo isolated in southeastern brazil during the early years of the outbreak, 1999-2006.outbreaks of a vesiculopustular disease in dairy cattle and milkers have been frequently reported in brazil since 1999 when the vaccinia virus strain cantagalo was first isolated in the state of rio de janeiro. however, the genomic diversity of the viral isolates associated with these outbreaks is not well known, particularly in the southeastern states that represent the focal point of virus spread to other regions. here, we report the genomic sequences and an analysis of the polymorphic site pr ...202133566940
a systemically deliverable vaccinia virus with increased capacity for intertumoral and intratumoral spread effectively treats pancreatic cancer.pancreatic cancer remains one of the most lethal cancers and is refractory to immunotherapeutic interventions. oncolytic viruses are a promising new treatment option, but current platforms demonstrate limited efficacy, especially for inaccessible and metastatic cancers that require systemically deliverable therapies. we recently described an oncolytic vaccinia virus (vv), vvlδtkδn1l, which has potent antitumor activity, and a regime to enhance intravenous delivery of vv by pharmacological inhibi ...202133500259
cd8 t cells show protection against highly pathogenic simian immunodeficiency virus (siv) after vaccination with siv gene-expressing bcg prime and vaccinia virus/sendai virus vector boosts.toward development of a dual vaccine for human immunodeficiency virus (hiv)-1 and tuberculosis infections, we developed a urease-deficient bacillus calmette-guérin (bcg) strain tokyo172 (bcgδurease) to enhance its immunogenicity. bcgδurease expressing simian immunodeficiency virus (siv) gag induced bcg antigen-specific cd4+ and cd8+ t cells more efficiently, and more gag-specific cd8+ t cells. we evaluated its protective efficacy against siv infection in cynomolgus monkeys of asian origin, shown ...202033087465
the vaccinia virus based sementis copenhagen vector vaccine against zika and chikungunya is immunogenic in non-human primates.the sementis copenhagen vector (scv) is a new vaccinia virus-derived, multiplication-defective, vaccine technology assessed herein in non-human primates. indian rhesus macaques (macaca mulatta) were vaccinated with a multi-pathogen recombinant scv vaccine encoding the structural polyproteins of both zika virus (zikv) and chikungunya virus (chikv). after one vaccination, neutralising antibody responses to zikv and four strains of chikv, representative of distinct viral genotypes, were generated. ...202032550013
evaluation of heterologous prime-boost vaccination strategies using chimpanzee adenovirus and modified vaccinia virus for tb subunit vaccination in rhesus macaques.tuberculosis (tb) still is the principal cause of death from infectious disease and improved vaccination strategies are required to reduce the disease burden and break tb transmission. here, we investigated different routes of administration of vectored subunit vaccines based on chimpanzee-derived adenovirus serotype-3 (chad3) for homologous prime-boosting and modified vaccinia virus ankara (mva) for heterologous boosting with both vaccine vectors expressing the same antigens from mycobacterium ...202032435513
innate and secondary humoral responses are improved by increasing the time between mva vaccine immunizations.comprehending the mechanisms behind the impact of vaccine regimens on immunity is critical for improving vaccines. indeed, the time-interval between immunizations may influence b and t cells, as well as innate responses. we compared two vaccine schedules using cynomolgus macaques immunized with an attenuated vaccinia virus. two subcutaneous injections 2 weeks apart led to an impaired secondary antibody response and similar innate myeloid responses to both immunizations. in contrast, a delayed bo ...202032218996
a new oncolytic vacciniavirus augments antitumor immune responses to prevent tumor recurrence and metastasis after surgery.local recurrence and remote metastasis are major challenges to overcome in order to improve the survival of patients with cancer after surgery. oncolytic viruses are a particularly attractive option for prevention of postsurgical disease as they offer a non-toxic treatment option that can directly target residual tumor deposits and beneficially modulate the systemic immune environment that is suppressed post surgery and allows residual disease escape from control. here, we report that a novel va ...202032217766
molecular and biological characterization of a cervidpoxvirus isolated from moose with necrotizing dermatitis.cervidpoxvirus is one of the more recently designated genera within the subfamily chordopoxvirinae, with deerpox virus (dpv) as the only recognized species to date. in this study, the authors describe spontaneous disease and infection in the north american moose (alces americanus) by a novel cervidpoxvirus, here named moosepox virus (mpv). three 4-month-old moose calves developed a multifocal subacute-to-chronic, necrotizing, suppurative-to-granulomatous dermatitis that affected the face and the ...202032096438
field trial vaccination against cowpox in two alpaca herds.in europe, cowpox virus (cpxv) infection in south american camelids occurs as a so-called spill-over infection. although infected animals generally have a mild form of the disease and survive, cases of fatal generalised cpxv infection have also been described. prevention by prophylactic vaccination is the only way to protect animals from disease. in the present study, modified vaccinia virus ankara (mva) vaccine, which has been successfully used in many animal species, was used in a prime-boost ...202032093320
repair of a previously uncharacterized second host-range gene contributes to full replication of modified vaccinia virus ankara (mva) in human cells.modified vaccinia virus ankara (mva), a widely used vaccine vector for expression of genes of unrelated pathogens, is safe, immunogenic, and can incorporate large amounts of added dna. mva was derived by extensively passaging the chorioallantois vaccinia virus ankara (cva) vaccine strain in chicken embryo fibroblasts during which numerous mutations and deletions occurred with loss of replicative ability in most mammalian cells. restoration of the deleted c12l gene, encoding serine protease inhib ...202032019881
molecular and genomic characterization of a novel equine molluscum contagiosum-like virus.cases of pox-like lesions in horses and donkeys have been associated with poxviruses belonging to different genera of the family poxviridae. these include the orthopoxviruses vaccinia virus (vacv), horsepoxvirus (hpxv) and cowpoxvirus (cpxv), as well as a potentially novel parapoxvirus and molluscum contagiosum virus (mocv). however, with the exception of vacv, hpxv and cpxv, the genomic characterization of the causative agents remains largely elusive with only single short genome fragments avai ...202031922947
recombinant modified vaccinia virus ankara (mva) vaccines efficiently protect cockatiels against parrot bornavirus infection and proventricular dilatation disease.parrot bornaviruses (pabvs) are the causative agents of proventricular dilatation disease (pdd), a chronic and often fatal neurologic disorder in psittaciformes. the disease is widely distributed in private parrot collections and threatens breeding populations of endangered species. thus, immunoprophylaxis strategies are urgently needed. in previous studies we demonstrated a prime-boost vaccination regime using modified vaccinia virus ankara (mva) and newcastle disease virus (ndv) constructs exp ...201931817690
mva-vectored pentameric complex (pc) and gb vaccines improve pregnancy outcome after guinea pig cmv challenge, but only gb vaccine reduces vertical transmission.(1) background: a congenital cytomegalovirus (ccmv) vaccine is a major research priority, but the essential glycoprotein target(s) remain unclear. we compared cmv gb (gpgb), gh/gl (gp75/gl), and pentameric complex (gppc, composed of gh/gl/gp129/gp131/gp133) vaccines in a guinea pig cmv (gpcmv) congenital infection model. (2) methods: modified vaccinia virus ankara (mva) vaccines expressing gpcmv glycoproteins were used to immunize gpcmv-seronegative, female hartley guinea pigs (three-dose series ...201931739399
activation of rnase l in egyptian rousette bat-derived roni/7 cells is dependent primarily on oas3 and independent of mavs signaling.bats are reservoirs for many rna viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. it has been suggested that differences in innate immunity are responsible. the antiviral oas-rnase l pathway is well characterized in humans, but there is little known about its activation and antiviral activity in bats. during infection, oass, upon sensing double-stranded rna (dsrna), produce 2'-5' oligoadenylates (2-5a), leading to activation of rnase l which degrades v ...201931719180
exposure of free-ranging capybaras (hydrochoerus hydrochaeris) to the vaccinia virus.the aim of this study was to evaluate the possibility of free-ranging animals/hunting dogs as sources of infection in the vaccinia virus (vacv) transmission chain. serological, cell culture and molecular assays were conducted in 56 free-ranging animals and 22 hunting dogs. elisa/neutralizing assays showed that two (2.5%) capybaras (hydrochoerus hydrochaeris) had anti-opv positive antibodies, while all samples tested negative through pcr/cell culture. after being hit by cars on roads, capybaras t ...202031574216
common vole (microtus arvalis) and bank vole (myodes glareolus) derived permanent cell lines differ in their susceptibility and replication kinetics of animal and zoonotic viruses.pathogenesis and reservoir host adaptation of animal and zoonotic viruses are poorly understood due to missing adequate cell culture and animal models. the bank vole (myodes glareolus) and common vole (microtus arvalis) serve as hosts for a variety of zoonotic pathogens. for a better understanding of virus association to a putative animal host, we generated two novel cell lines from bank voles of different evolutionary lineages and two common vole cell lines and assayed their susceptibility, rep ...201931513859
successful establishment of a reverse genetic system for qx-type infectious bronchitis virus and technical improvement of the rescue procedure.in this study, a pathogenic avian infectious bronchitis virus (ibv) qx-type strain yn was successfully rescued by vaccinia virus based reverse genetic technology. ten fragments contiguously spanning the complete ibv genome were amplified and cloned into the vaccinia virus genome by homologous recombination. the full-length genomic cdna was transcribed in vitro, and its transcript was transfected into bhk-21/n cells that could stably express ibv n protein. at 48 h post transfection, the culture m ...201931430502
human immunodeficiency virus c.1086 envelope gp140 protein boosts following dna/modified vaccinia virus ankara vaccination fail to enhance heterologous anti-v1v2 antibody response and protection against clade c simian-human immunodeficiency virus challenge.the rv144 human immunodeficiency virus type 1 (hiv-1) vaccine trial showed a strong association between anti-gp70 v1v2 scaffold (v1v2) and anti-v2 hot spot peptide (v2 hs) antibody responses and reduced risk of hiv infection. accordingly, a primary goal for hiv vaccines is to enhance the magnitude and breadth of v1v2 and v2 hs antibody responses in addition to neutralizing antibodies. here, we tested the immunogenicity and efficacy of hiv-1 c.1086 gp140 boosts administered sequentially after pri ...201931341049
spi-1 is a missing host-range factor required for replication of the attenuated modified vaccinia ankara (mva) vaccine vector in human cells.modified vaccinia virus ankara (mva) is the leading poxvirus vector for development of vaccines against diverse infectious diseases. this distinction is based on high expression of proteins and good immunogenicity despite an inability to assemble infectious progeny in human cells, which together promote efficacy and safety. nevertheless, the basis for the host-range restriction is unknown despite past systematic attempts to identify the relevant missing viral gene(s). the search for host-range f ...201931145755
therapeutic monoclonal antibodies for ebola virus infection derived from vaccinated humans.we describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing ebola virus glycoprotein (ebov gp) and boosted with modified vaccinia virus ankara. among 82 antibodies isolated from peripheral blood b cells, almost half neutralized gp pseudotyped influenza virus. the antibody response was diverse in gene usage and epitope recognition. although close to germline in sequence, neutralizing antibodies with binding affinities in the nano- ...201930943399
identification of cp77 as the third orthopoxvirus samd9 and samd9l inhibitor with unique specificity for a rodent samd9l.orthopoxviruses (opxvs) have a broad host range in mammalian cells, but chinese hamster ovary (cho) cells are nonpermissive for vaccinia virus (vacv). here, we revealed a species-specific difference in host restriction factor samd9l as the cause for the restriction and identified orthopoxvirus cp77 as a unique inhibitor capable of antagonizing chinese hamster samd9l (chsamd9l). two known vacv inhibitors of samd9 and samd9l (samd9&l), k1 and c7, can bind human and mouse samd9&l, but neither can b ...201930918078
chicken embryonic-stem cells are permissive to poxvirus recombinant vaccine vectors.the discovery of mammalian pluripotent embryonic stem cells (esc) has revolutionised cell research and regenerative medicine. more recently discovered chicken esc (cesc), though less intensively studied, are increasingly popular as vaccine substrates due to a dearth of avian cell lines. information on the comparative performance of cesc with common vaccine viruses is limited. using rna-sequencing, we compared cesc transcriptional programmes elicited by stimulation with chicken type i interferon ...201930897824
selection of vaccinia virus-neutralizing antibody from a phage-display human-antibody library.although smallpox was eradicated in 1980, it is still considered a potential agent of biowarfare and bioterrorism. smallpox has the potential for high mortality rates along with a major public health impact, eventually causing public panic and social disruption. passive administration of neutralizing monoclonal antibodies (mabs) is an effective intervention for various adverse reactions caused by vaccination and the unpredictable nature of emerging and bioterrorist-related infections. currently, ...201930856707
bridging vaccine-induced hiv-1 neutralizing and effector antibody responses in rabbit and rhesus macaque animal models.studies in animal models are essential prerequisites for clinical trials of candidate hiv vaccines. small animals, such as rabbits, are used to evaluate promising strategies prior to further immunogenicity and efficacy testing in nonhuman primates. our goal was to determine how hiv-specific vaccine-elicited antibody responses, epitope specificity, and fc-mediated functions in the rabbit model can predict those in the rhesus macaque (rm) model. detailed comparisons of the hiv-1-specific igg respo ...201930842326
nk cell immune responses differ after prime and boost vaccination.a better understanding of innate responses induced by vaccination is critical for designing optimal vaccines. here, we studied the diversity and dynamics of the nk cell compartment after prime-boost immunization with the modified vaccinia virus ankara using cynomolgus macaques as a model. mass cytometry was used to deeply characterize blood nk cells. the nk cell subphenotype composition was modified by the prime. certain phenotypic changes induced by the prime were maintained over time and, as a ...201930794328
clade c hiv-1 envelope vaccination regimens differ in their ability to elicit antibodies with moderate neutralization breadth against genetically diverse tier 2 hiv-1 envelope variants.the goals of preclinical hiv vaccine studies in nonhuman primates are to develop and test different approaches for their ability to generate protective immunity. here, we compared the impact of 7 different vaccine modalities, all expressing the hiv-1 1086.c clade c envelope (env), on (i) the magnitude and durability of antigen-specific serum antibody responses and (ii) autologous and heterologous neutralizing antibody capacity. these vaccination regimens included immunization with different comb ...201930651354
novel modified vaccinia virus ankara vector expressing anti-apoptotic gene b13r delays apoptosis and enhances humoral responses.modified vaccinia virus ankara (mva), an attenuated poxvirus, has been developed as a potential vaccine vector for use against cancer and multiple infectious diseases, including human immunodeficiency virus (hiv). mva is highly immunogenic and elicits strong cellular and humoral responses in preclinical models and humans. however, there is potential to further enhance the immunogenicity of mva, as mva-infected cells undergo rapid apoptosis, leading to faster clearance of recombinant antigens and ...201930541829
dynamic transcriptome profiling dataset of vaccinia virus obtained from long-read sequencing techniques.poxviruses are large dna viruses that infect humans and animals. vaccinia virus (vacv) has been applied as a live vaccine for immunization against smallpox, which was eradicated by 1980 as a result of worldwide vaccination. vacv is the prototype of poxviruses in the investigation of the molecular pathogenesis of the virus. short-read sequencing methods have revolutionized transcriptomics; however, they are not efficient in distinguishing between the rna isoforms and transcript overlaps. long-rea ...201830476066
priming with a potent hiv-1 dna vaccine frames the quality of immune responses prior to a poxvirus and protein boost.the use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of hiv-1 vaccine candidates in nonhuman primates. in order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. three groups of rhesus macaques were each primed with the same dna vaccine encoding gag, pol, nef, and gp140. the groups were then boosted with either the vaccinia virus strain nyvac or a variant with improve ...201930429343
replication-competent nyvac-kc yields improved immunogenicity to hiv-1 antigens in rhesus macaques compared to nonreplicating nyvac.as part of the continuing effort to develop an effective hiv vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the rv144 phase iii clinical trial. the construct, nyvac-kc, is a replication-competent, attenuated recombinant of the vaccinia virus strain nyvac. nyvac is a vector that has been used in many previous clinical studies but is replication deficient. here, we report a side-by-side comparison of replication-restricted nyvac and rep ...201930429340
whole genome characterization of orthopoxvirus (opv) abatino, a zoonotic virus representing a putative novel clade of old world orthopoxviruses.orthopoxviruses (opvs) are diffused over the complete eurasian continent, but previously described strains are mostly from northern europe, and few infections have been reported from italy. here we present the extended genomic characterization of opv abatino, a novel opv isolated in italy from an infected tonkean macaque, with zoonotic potential. phylogenetic analysis based on 102 conserved opv genes (core gene set) showed that opv abatino is most closely related to the ectromelia virus species ...201830301229
tracking modified vaccinia virus ankara in the chicken embryo: in vivo tropism and pathogenesis of egg infections.the modified vaccinia virus ankara (mva) is a highly attenuated vaccinia virus serving as a promising vector vaccine platform to develop vaccines against infectious diseases. in contrast to the well-established replication deficiency and safety of mva in mammals, much less is known about mva infection in avian hosts. here, we used a recombinant mva expressing fluorescent reporter proteins under transcriptional control of specific viral early and late promoters to study in vivo tropism, distribut ...201830149505
removal of the c6 vaccinia virus interferon-β inhibitor in the hepatitis c vaccine candidate mva-hcv elicited in mice high immunogenicity in spite of reduced host gene expression.hepatitis c virus (hcv) represents a major global health problem for which a vaccine is not available. modified vaccinia virus ankara (mva)-hcv is a unique hcv vaccine candidate based in the modified vaccinia virus ankara (mva) vector expressing the nearly full-length genome of hcv genotype 1a that elicits cd8⁺ t-cell responses in mice. with the aim to improve the immune response of mva-hcv and because of the importance of interferon (ifn) in hcv infection, we deleted in mva-hcv the vaccinia vir ...201830096846
short communication: parapoxvirus and orthopoxvirus coinfection in milk of naturally infected cows.several studies have shown the occurrence of poxvirus infections associated with exanthematic lesions in cattle from many brazilian states. coinfection between viruses belonging to 2 genera, orthopoxvirus (opxv) and parapoxvirus (ppv), was already identified from the lesions of affected cows and humans. the dna and infectious viral particles of vaccinia virus, an opxv, have been detected in milk of naturally and experimentally infected cows. however, to date no reports have described the detecti ...201830007812
experimental infection of dromedaries with middle east respiratory syndrome-coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4.middle east respiratory syndrome (mers) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. in the current study, tissues of eight dromedaries receiving inoculation of mers-coronavirus (mers-cov) after recombinant modified-vaccinia-virus-ankara (mva-s)-vaccination (n = 4), mva-vaccinat ...201829950581
immunogenicity of propagation-restricted vesicular stomatitis virus encoding ebola virus glycoprotein in guinea pigs.vesicular stomatitis virus (vsv) expressing the ebola virus (ebov) glycoprotein (gp) in place of the vsv glycoprotein g (vsv/ebov-gp) is a promising ebov vaccine candidate which has already entered clinical phase 3 studies. although this chimeric virus was tolerated overall by volunteers, it still caused viremia and adverse effects such as fever and arthritis, suggesting that it might not be sufficiently attenuated. in this study, the vsv/ebov-gp vector was further modified in order to achieve a ...201829869979
the immune response of rhesus macaques to novel vaccines comprising hepatitis b virus s, pres1, and core antigens.therapeutic vaccines represent a unique approach to hepatitis b virus (hbv) treatment and have the potential to induce long-term control of infection. this study explored the immune responses of rhesus macaques to novel vaccines comprising the s, pres1, and core antigens of the hbv that showed promise as prophylactic and therapeutic approaches in a mouse model. the tested vaccines included two dna vaccines (pvrc-ss1, pvrc-cs1), an hbv particle subunit (hbss1) vaccine and the recombinant vaccinia ...201829778513
bovine vaccinia: insights into the disease in cattle.bovine vaccinia (bv), caused byvaccinia virus(vacv), is a zoonosis characterized by exanthematous lesions in the teats of dairy cows and the hands of milkers and is an important public health issue. severe vacv-induced lesions in the teats and udder of cows and buffaloes could lead to mastitis and other secondary infections, thereby reducing productivity and resulting in economic losses to the dairy industry. in brazil, bv re-emerged in the late 1990s and is now endemic in most of the brazilian ...201829522489
prime and boost vaccination elicit a distinct innate myeloid cell immune response.understanding the innate immune response to vaccination is critical in vaccine design. here, we studied blood innate myeloid cells after first and second immunization of cynomolgus macaques with the modified vaccinia virus ankara. the inflammation at the injection site was moderate and resolved faster after the boost. the blood concentration of inflammation markers increased after both injections but was lower after the boost. the numbers of neutrophils, monocytes, and dendritic cells were trans ...201829449630
vaccinia virus in feces and urine of wild rodents from são paulo state, brazil.the origin of vaccinia virus (vacv) outbreaks in brazil remains unknown, but since the isolation of vacv in mus musculus mice during a zoonotic outbreak affecting cattle and milkers, peridomestic rodents have been suggested to be a link between cows and wild animals. considering that experimentally infected mice eliminate viral particles in their feces, we investigated the presence of vacv in the feces and urine of wild rodents that were captured in the forest areas surrounding milking farms in ...201829360742
maternal hiv-1 env vaccination for systemic and breast milk immunity to prevent oral shiv acquisition in infant macaques.mother-to-child transmission (mtct) of human immunodeficiency virus type 1 (hiv-1) contributes to an estimated 150,000 new infections annually. maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit hiv-1 infection of infants through breastfeeding. in the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified v ...201829359183
vaccinia virus in blood samples of humans, domestic and wild mammals in brazil.outbreaks of vaccinia virus (vacv) affecting cattle and humans have been reported in brazil in the last 15 years, but the origin of outbreaks remains unknown. although vacv dna have been already detected in mice (mus musculus), opossums (didelphis albiventris) and dogs during vacv zoonotic outbreaks, no transmission to cattle or humans from any of these were reported during brazilian outbreaks. in this work, we assessed the pcr positivity to vacv in blood samples of cows and other domestic mamma ...201829346277
buffalopox.buffalopox is a contagious viral disease affecting milch buffaloes (bubalus bubalis) and, rarely, cows. the disease has zoonotic implications, as outbreaks are frequently associated with human infections, particularly in the milkers. buffalopox is associated with high morbidity (80%). the clinical symptoms of the disease are characterized by wartline lesions on the udder, teats, inguinal region, base of the ears, and over the parotid. in the severe form, generalized rash is observed. although th ...201829323851
antiviral activity and metal ion-binding properties of some 2-hydroxy-3-methoxyphenyl acylhydrazones.here we report on the results obtained from an antiviral screening, including herpes simplex virus, vaccinia virus, vesicular stomatitis virus, coxsackie b4 virus or respiratory syncytial virus, parainfluenza-3 virus, reovirus-1 and punta toro virus, of three 2-hydroxy-3-methoxyphenyl acylhydrazone compounds in three cell lines (i.e. human embryonic lung fibroblast cells, human cervix carcinoma cells, and african green monkey kidney cells). interesting antiviral ec50 values are obtained against ...201829209895
dairy production practices and associated risks for bovine vaccinia exposure in cattle, brazil.a cross-sectional serosurvey was performed to identify environmental features or practices of dairy farms associated with risk for exposure to vaccinia-like viruses in dairy cattle in brazil. sera from 103 cows from 18 farms in minas gerais state were examined fororthopoxvirus-neutralizing antibodies. a database of 243 binary or multiple-selection categorical variables regarding the physical features and surrounding ecology of each property was obtained. thirteen of 46 presumptive predictor vari ...201729158908
vaccinia virus natural infections in brazil: the good, the bad, and the ugly.the orthopoxviruses (opv) comprise several emerging viruses with great importance to human and veterinary medicine, including vaccinia virus (vacv), which causes outbreaks of bovine vaccinia (bv) in south america. historically, vacv is the most comprehensively studied virus, however, its origin and natural hosts remain unknown. vacv was the primary component of the smallpox vaccine, largely used during the smallpox eradication campaign. after smallpox was declared eradicated, the vaccination tha ...201729140260
hiv-1 gp120 and modified vaccinia virus ankara (mva) gp140 boost immunogens increase immunogenicity of a dna/mva hiv-1 vaccine.an important goal of human immunodeficiency virus (hiv) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. one novel approach comprises priming with dna and boosting with modified vaccinia virus ankara (mva) expressing hiv-1 env on virus-like particles. in this study, we evaluated whether the addition of a gp120 protein in alum or mva-expressed secreted gp140 (mvagp140) could improve immunogenicity of a dna prime-mva boost vaccine. five rhesus macaqu ...201729021394
oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (raboral v-rg®): a global review.raboral v-rg® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (v-rg). approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (orv) was released into the environment to immunize wildlife populations against rabies. v-rg is genetically ...201728938920
characterization of a pkr inhibitor from the pathogenic ranavirus, ambystoma tigrinum virus, using a heterologous vaccinia virus system.ambystoma tigrinum virus (atv) (family iridoviridae, genus ranavirus) was isolated from diseased tiger salamanders (ambystoma tigrinum stebbinsi) from the san rafael valley in southern arizona, usa in 1996. genomic sequencing of atv, as well as other members of the genus, identified an open reading frame that has homology to the eukaryotic translation initiation factor, eif2α (atv eif2α homologue, vif2αh). therefore, we asked if the atv vif2αh could also inhibit pkr. to test this hypothesis, the ...201728919326
immunogenicity and efficacy of dna/mva hiv vaccines in rhesus macaque models.despite 30 years of research on hiv, a vaccine to prevent infection and limit disease progression remains elusive. the rv144 trial showed moderate, but significant protection in humans and highlighted the contribution of antibody responses directed against hiv envelope as an important immune correlate for protection. efforts to further build upon the progress include the use of a heterologous prime-boost regimen using dna as the priming agent and the attenuated vaccinia virus, modified vaccinia ...201728838267
the impact of poxvirus vector priming, protein co-administration, and vaccine intervals on hiv gp120 vaccine-elicited antibody magnitude and function in infant macaques.despite success in reducing vertical hiv transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (mtct) of hiv in infants. thus, a pediatric vaccine is needed to eradicate oral hiv infections in newborns and infants. utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) hiv env protein only; (ii) a poxvirus vector (mva)-hiv e ...201728814388
ecological niche modeling to determine potential niche of vaccinia virus: a case only study.emerging and understudied pathogens often lack information that most commonly used analytical tools require, such as negative controls or baseline data; thus, new analytical strategies are needed to analyze transmission patterns and drivers of disease emergence. zoonotic infections with vaccinia virus (vacv) were first reported in brazil in 1999, vacv is an emerging zoonotic orthopoxvirus, which primarily infects dairy cattle and farmers in close contact with infected cows. prospective studies o ...201728784125
species specificity of vaccinia virus complement control protein towards bovine classical pathway is governed primarily by direct interaction of its acidic residues with factor i.poxviruses display species tropism - variola virus is a human-specific virus, while vaccinia virus causes repeated outbreaks in dairy cattle. consistent with this, variola virus complement regulator spice exhibit selectivity in inhibiting the human alternative complement pathway and vaccinia virus complement regulator vcp display selectivity in inhibiting the bovine alternative complement pathway. in the present study, we examined the species-specificity of vcp and spice towards the classical pa ...201728724763
vaccinia virus detection in dairy products made with milk from experimentally infected cows.vaccinia virus (vacv) is the agent of bovine vaccinia (bv), an emerging zoonosis that causes exanthematic lesions on the teats of dairy cows and on the hands of milkers. the virus has been detected in the milk of naturally infected cows. the objective of this study was to investigate and quantify vacv dna as well as the presence of infectious virus particles in samples of cheese curd, cheese whey and pasteurized milk produced using milk from cows experimentally inoculated with vacv-gp2, a brazil ...201728649801
bovine vaccinia: inactivated vaccinia virus vaccine induces protection in murine model.bovine vaccinia (bv), caused by vaccinia virus (vacv), is a zoonosis characterized by exanthematous lesions on the teats of dairy cows and the milkers' hands. since 1999, due to the occurrence of many bv outbreaks in dairy farms across all brazilian regions, there is a need to improve the control and prevention measures of the disease. vaccination is one of the major tools to prevent viral diseases, and it could be an alternative for bv prevention. the main objective of this study was the develo ...201728532811
subclinical bovine vaccinia: an important risk factor in the epidemiology of this zoonosis in cattle.bovine vaccinia (bv) is a zoonosis caused by vaccinia virus (vacv) that mainly affects lactating cows and dairy farm milkers. the epidemiological role(s) of other cattle categories such as dry cows, bulls, and heifers in bv remains unclear. this study was performed to investigate vacv in affected dairy cattle herds and perifocal farms during an outbreak in brazil. crusts from lesions of cows' teats were collected from all farms with bv outbreaks. milk, feces, blood, and serum were collected from ...201728502903
transient dominant host-range selection using chinese hamster ovary cells to generate marker-free recombinant viral vectors from vaccinia virus.recombinant vaccinia viruses (rvacvs) are promising antigen-delivery systems for vaccine development that are also useful as research tools. two common methods for selection during construction of rvacv clones are (i) co-insertion of drug resistance or reporter protein genes, which requires the use of additional selection drugs or detection methods, and (ii) dominant host-range selection. the latter uses vacv variants rendered replication-incompetent in host cell lines by the deletion of host-ra ...201728403810
absence of vaccinia virus detection in a remote region of the northern amazon forests, 2005-2015.vaccinia virus (vacv) circulates in brazil and other south america countries and is responsible for a zoonotic disease that usually affects dairy cattle and humans, causing economic losses and impacting animal and human health. furthermore, it has been detected in wild areas in the brazilian amazon. to better understand the natural history of vacv, we investigated its circulation in wildlife from french guiana, a remote region in the northern amazon forest. elisa and plaque reduction neutralizat ...201728389806
monocytic myeloid-derived suppressor cells regulate t-cell responses against vaccinia virus.vaccinia virus (vv) can potently activate nk- and t-cell responses, leading to efficient viral control and generation of long-lasting protective immunity. however, immune responses against viral infections are often tightly controlled to avoid collateral damage and systemic inflammation. we have previously shown that granulocytic myeloid derived suppressor cells (g-mdscs) can suppress the nk-cell response to vv infection. it remains unknown what regulates t-cell responses to vv infection in vivo ...201728383204
generating recombinant vesicular stomatitis viruses for use as vaccine platforms.the unique properties of vesicular stomatitis virus (vsv) make it a promising vaccine platform. with the advent of plasmid-based approaches to generate recombinant vsv viruses that express glycoproteins of other viruses, researchers now have the means to generate vaccine candidates targeting a variety of human pathogens. this chapter gives a general overview of the workings of vsv as a vaccine platform and provides a detailed protocol for the generation of recombinant vsv from plasmids.201728374251
development of recombinant canarypox viruses expressing immunogens.canarypox viruses (cnpv) are excellent candidates to develop recombinant vector vaccines due to both their capability to induce protective immune responses and their incompetence to replicate in mammalian cells (safety profile). in addition, cnpv and the derived recombinants can be manipulated under biosafety level 1 conditions. there is no commercially available system to obtain recombinant cnpv; however, the methodology and tools required to develop recombinant vaccinia virus (vv), prototype o ...201728374241
diclofenac-based hydrazones and spirothiazolidinones: synthesis, characterization, and antimicrobial properties.we report here the synthesis, structural characterization, and biological evaluation of novel diclofenac-based hydrazone (4a-f) and spirothiazolidinone (5a-f, 6a-f) derivatives designed as potential antimicrobial agents. the compounds were evaluated in vitro for their antiviral activity against a wide spectrum of dna and rna viruses. they were further screened in vitro against different strains of bacteria and fungi. the hydrazone derivatives, 4a and 4c-f, were found to be active against herpesv ...201728370198
vaccinia virus evasion of regulated cell death.regulated cell death is a powerful anti-viral mechanism capable of aborting the virus replicative cycle and alerting neighbouring cells to the threat of infection. the biological importance of regulated cell death is illustrated by the rich repertoire of host signalling cascades causing cell death and by the multiple strategies exhibited by viruses to block death signal transduction and preserve cell viability. vaccinia virus (vacv), a poxvirus and the vaccine used to eradicate smallpox, encodes ...201728366525
oncolytic virotherapy and gene therapy strategies for hepatobiliary cancers.advanced liver cancers and biliary cancers represent diseases with dismal prognosis because of frequent local invasion and metastasis. effective therapeutic agents for these cancers have not been established. oncolytic viruses (ovs) constitute a novel class of promising, selective anticancer agents and recent studies have elucidated their unique features. moreover, clinical trials are demonstrating promising results. numerous ovs are being tested in preclinical models of hepatocellular carcinoma ...201728359239
identification of novel 5,6-dimethoxyindan-1-one derivatives as antiviral agents.discovery of novel antiviral agents is essential because viral infection continues to threaten human life globally. various heterocyclic small molecules have been developed as antiviral agents. the 5,6-dimethoxy indan-1-one nucleus is of considerable interest as this ring is the key constituent in a range of bioactive compounds, both naturally occurring and synthetic, and often of considerable complexity.201728359234
cytosolic dna sensor-initiated innate immune responses in mouse ovarian granulosa cells.viral infections of the ovary may perturb ovarian functions. however, the mechanisms underlying innate immune responses in the ovary are poorly understood. the present study demonstrates that cytosolic viral dna sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. the cytosolic dna sensors p204 and cgas and their common signaling adaptor stimulator of interferon (ifn) genes (sting) were constitutively expressed in granulosa cells. ...201728351933
rational combination of oncolytic vaccinia virus and pd-l1 blockade works synergistically to enhance therapeutic efficacy.both anti-pd1/pd-l1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. here we hypothesized that an oncolytic poxvirus would attract t cells into the tumour, and induce pd-l1 expression in cancer and immune cells, leading to more susceptible targets for anti-pd-l1 immunotherapy. our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector t cells and induces pd-l1 e ...201728345650
gastrointestinal microbiome dysbiosis in infant mice alters peripheral cd8(+) t cell receptor signaling.we recently reported that maternal antibiotic treatment (mat) of mice in the last days of pregnancy and during lactation dramatically alters the density and composition of the gastrointestinal microbiota of their infants. mat infants also exhibited enhanced susceptibility to a systemic viral infection and altered adaptive immune cell activation phenotype and function. cd8(+) effector t cells from mat infants consistently demonstrate an inability to sustain interferon gamma (ifn-γ) production in ...201728337207
monkeypox virus host factor screen in haploid cells identifies essential role of garp complex in extracellular virus formation.monkeypox virus (mpxv) is a human pathogen that is a member of the orthopoxvirus genus, which includes vaccinia virus and variola virus (the causative agent of smallpox). human monkeypox is considered an emerging zoonotic infectious disease. to identify host factors required for mpxv infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. the screen revealed several candidate genes, including those involved in golgi trafficking, glycosaminoglycan biosynthesis ...201728331092
current status of clinical trials assessing oncolytic virus therapy for urological cancers.oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. notably, t-vec (talimogene laherparepvec, formerly called oncovex(gm)(-)(csf) ), an oncolytic herpes simplex virus type 1, was approved by the us food and drug administration for the treatment of inoperable melanoma in october 2015, and was subsequently approved in europe and australia in 2016 ...201728326624
detection and molecular characterization of zoonotic poxviruses circulating in the amazon region of colombia, 2014.during 2014, cutaneous lesions were reported in dairy cattle and farmworkers in the amazon region of western colombia. samples from 6 patients were analyzed by serologic and pcr testing, and results demonstrated the presence of vaccinia virus and pseudocowpox virus. these findings highlight the need for increased poxvirus surveillance in colombia.201728322708
triad of human cellular proteins, irf2, fam111a, and rfc3, restrict replication of orthopoxvirus spi-1 host-range mutants.viruses and their hosts can reach balanced states of evolution ensuring mutual survival, which makes it difficult to appreciate the underlying dynamics. to uncover hidden interactions, virus mutants that have lost defense genes may be used. deletion of the gene that encodes serine protease inhibitor 1 (spi-1) of rabbitpox virus and vaccinia virus, two closely related orthopoxviruses, prevents their efficient replication in human cells, whereas certain other mammalian cells remain fully permissiv ...201728320935
dynamic monitoring of membrane nanotubes formation induced by vaccinia virus on a high throughput microfluidic chip.membrane nanotubes (mnts) are physical connections for intercellular communication and induced by various viruses. however, the formation of vaccinia virus (vacv)-induced mnts has never been studied. in this report, vacv-induced mnts formation process was monitored on a microfluidic chip equipped with a series of side chambers, which protected mnts from fluidic shear stress. mnts were formed between susceptible cells and be facilitated by vacv infection through three patterns. the formed mnts va ...201728317863
deletion of f4l (ribonucleotide reductase) in vaccinia virus produces a selective oncolytic virus and promotes anti-tumor immunity with superior safety in bladder cancer models.bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. in particular, standard of care for high-grade disease, bacillus calmette-guérin (bcg), fails in 30% of patients. we have generated a novel oncolytic vaccinia virus (vacv) by mutating the f4l gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (rrm2). the f4l-deleted vacvs are highly atten ...201728289079
il-18-dependent nkg2d ligand upregulation on accessory cells is mediated by the pi3k/gsk-3 pathway.nk cells are critical for the control of viral infections. studies have shown that efficient nk cell activation in response to infection with vv in vivo requires multiple pathways, including the nkg2d pathway. we have recently shown that il-18 is necessary for the activation of nk cells through upregulation of the nkg2d ligand rae-1 on dcs upon vv infection. however, how il-18r signaling on the accessory cells contributes to rae-1 up-regulation remains to be defined. in this study, we found il-1 ...201728283665
rna-seq based transcriptome analysis of the type i interferon host response upon vaccinia virus infection of mouse cells.vaccinia virus (vacv) encodes the soluble type i interferon (ifn) binding protein b18 that is secreted from infected cells and also attaches to the cell surface, as an immunomodulatory strategy to inhibit the host ifn response. by using next generation sequencing technologies, we performed a detailed rna-seq study to dissect at the transcriptional level the modulation of the ifn based host response by vacv and b18. transcriptome profiling of l929 cells after incubation with purified recombinant ...201728280747
vaccinia virus a6 is a two-domain protein requiring a cognate n-terminal domain for full viral membrane assembly activity.poxvirus virion biogenesis is a complex, multistep process, starting with the formation of crescent-shaped viral membranes, followed by their enclosure of viral core to form the spherical immature virions. crescent formation requires a group of proteins that are highly conserved among poxviruses, including a6 and a11 of vaccinia virus (vacv). to gain a better understanding of the molecular function of a6, we established a hela cell line that inducibly expressed vacv-a6, which allowed us to const ...201728275183
antibody recognition of immunodominant vaccinia virus envelope proteins.vaccinia virus (vacv) is an enveloped double stranded dna virus and the active ingredient of the smallpox vaccine. the systematic administration of this vaccine led to the eradication of circulating smallpox (variola virus, varv) from the human population. as a tribute to its success, global immunization was ended in the late 1970s. the efficacy of the vaccine is attributed to a robust production of protective antibodies against several envelope proteins of vacv, which cross-protect against infe ...201728271474
the vaccinia virus k7 protein promotes histone methylation associated with heterochromatin formation.it has been well established that many vaccinia virus proteins suppress host antiviral pathways by targeting the transcription of antiviral proteins, thus evading the host innate immune system. however, whether viral proteins have an effect on the host's overall cellular transcription is less understood. in this study we investigated the regulation of heterochromatin during vaccinia virus infection. heterochromatin is a highly condensed form of chromatin that is less transcriptionally active and ...201728257484
survival of tissue-resident memory t cells requires exogenous lipid uptake and metabolism.tissue-resident memory t (trm) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. however, the biological pathways that enable the long-term survival of trm cells are obscure. here we show that mouse cd8(+) trm cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (fabp4 and fabp5). we further show that ...201728219080
divergent roles of β- and γ-actin isoforms during spread of vaccinia virus.actin is a major component of the cytoskeleton and is present as two isoforms in non-muscle cells: β- and γ-cytoplasmic actin. these isoforms are strikingly conserved, differing by only four n-terminal amino acids. during spread from infected cells, vaccinia virus (vacv) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell-to-cell spread of infection. here we show that virus-tipped actin comets are composed of β- and γ-actin. we employed isoform- ...201728218453
ac dielectrophoretic manipulation and electroporation of vaccinia virus using carbon nanoelectrode arrays.this paper reports the capture and detection of vaccinia virus particles based on ac dielectrophoresis (dep) and electrochemical impedance measurements employing an embedded vertically aligned carbon nanofiber (vacnf) nanoelectrode array (nea) versus a macroscopic indium-tin-oxide (ito) transparent electrode in a "points-and-lid" configuration. the nano-dep device was fabricated by bonding two su-8 covered electrodes patterned using photolithography. the bottom electrode contains a 200 × 200 μm( ...201728211116
establishing elements of a synthetic biology platform for vaccinia virus production: biobrick™ design, serum-free virus production and microcarrier-based cultivation of cv-1 cells.vaccinia virus (vacv) is an established vector for vaccination and is beginning to prove effective as an oncolytic agent. industrial production of vacv stands to benefit in future from advances made by synthetic biology in genome engineering and standardisation. the cv-1 cell line can be used for vacv propagation and has been used extensively with the crispr/cas9 system for making precise edits of the vacv genome. here we take first steps toward establishing a scalable synthetic biology platform ...201728203643
virus-specific cd8(+) t cells infiltrate melanoma lesions and retain function independently of pd-1 expression.it is well known that cd8(+) tumor-infiltrating lymphocytes (tils) are correlated with positive prognoses in cancer patients and are used to determine the efficacy of immune therapies. although it is generally assumed that cd8(+) tils will be tumor-associated ag (taa) specific, it is unknown whether cd8(+) t cells with specificity for common pathogens also infiltrate tumors. if so, the presence of these t cells could alter the interpretation of prognostic and diagnostic til assays. we compared t ...201728202614
identification and characterization of orf virus 050 protein proteolysis.the orf virus 050 (orfv050) gene is located in the core region of the orfv genome. it is similar to vaccinia virus (vv) copenhagen l4r, and encodes the dna-binding virion core protein vp8, which has structures similar to the vv p25k core protein and may undergo similar proteolytic processing during virus assembly. three conserved ala-gly-x motifs at putative cleavage sites were identified in orfv050. to investigate the proteolysis of orfv050 and its participation in viral assembly, full-length a ...201728190135
proteomic screen for cellular targets of the vaccinia virus f10 protein kinase reveals that phosphorylation of mdia regulates stress fiber formation.vaccinia virus, a complex dsdna virus, is unusual in replicating exclusively within the cytoplasm of infected cells. although this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. the viral b1 kinase and h1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the f10 kinase. f10 is essential for virion morphogen ...201728183815
effects of mip-1α, mip-3α, and mip-3β on the induction of hiv gag-specific immune response with dna vaccines.transfection of dna vaccines with chemokines may recruit dendritic cells (dcs) locally to capture the antigenic genes and their gene products to generate enhanced cd8(+) cytotoxic t lymphocytes (ctls). in this study, we investigated the effects of macrophage inflammatory protein (mip)-1α, mip-3α, and mip-3β on human immunodeficiency virus (hiv) gag dna vaccination. the chemokine plasmids markedly enhanced the local infiltration of inflammatory cells and increased the presence of cd11c(+) b7.2(+) ...200728182892
chemotherapy enhances cd8(+) t cell-mediated antitumor immunity induced by vaccination with vaccinia virus.the use of immunotherapy or chemotherapy alone is generally ineffective against well-established tumors. to overcome this intrinsic resistance against therapy for tumors, we have attempted to combine immunotherapy with chemotherapy. in this study, we tried to induce a rapid antitumor effect via chemoimmunotherapy using a vaccinia viral vaccine as an immunotherapeutic agent with anticancer agents including epigallocatechin-3-gallate (egcg) and conventional anticancer drugs. although a combination ...200728182877
treating tumors with a vaccinia virus expressing ifnβ illustrates the complex relationships between oncolytic ability and immunogenicity.since previous work using a nonreplicating adenovirus-expressing mouse interferon-β (ad.mifnβ) showed promising preclinical activity, we postulated that a vector-expressing ifnβ at high levels that could also replicate would be even more beneficial. accordingly a replication competent, recombinant vaccinia viral vector-expressing mifnβ (vv.mifnβ) was tested. vv.mifnβ-induced antitumor responses in two syngeneic mouse flank models of lung cancer. although vv.mifnβ had equivalent in vivo efficacy ...201228160613
the vaccinia virus dna polymerase and its processivity factor.vaccinia virus is the prototypic poxvirus. the 192 kilobase double-stranded dna viral genome encodes most if not all of the viral replication machinery. the vaccinia virus dna polymerase is encoded by the e9l gene. sequence analysis indicates that e9 is a member of the b family of replicative polymerases. the enzyme has both polymerase and 3'-5' exonuclease activities, both of which are essential to support viral replication. genetic analysis of e9 has identified residues and motifs whose altera ...201728159613
myxoma virus dsrna binding protein m029  inhibits the type i ifn-induced antiviral state in a  highly species-specific fashion.myxoma virus (myxv) is leporipoxvirus that possesses a specific rabbit-restricted host tropism but exhibits a much broader  cellular host range in cultured cells. myxv is able to efficiently  block all aspects of the type i interferon (ifn)-induced  antiviral  state  in rabbit cells, partially in  human  cells  and  very  poorly  in  mouse  cells.  the mechanism(s) of this species-specific inhibition of  type i ifn-induced antiviral state is not well understood. here we demonstrate that myxv enc ...201728157174
investigating viruses during the transformation of molecular biology.this reflections article describes my early work on viral enzymes and the discovery of mrna capping, how my training in medicine and biochemistry merged as i evolved into a virologist, the development of viruses as vaccine vectors, and how scientific and technological developments during the 1970s and beyond set the stage for the interrogation of nearly every step in the reproductive cycle of vaccinia virus (vacv), a large dna virus with about 200 genes. the reader may view this article as a wor ...201728154190
entirely plasmid-based reverse genetics system for rotaviruses.rotaviruses (rvs) are highly important pathogens that cause severe diarrhea among infants and young children worldwide. the understanding of the molecular mechanisms underlying rv replication and pathogenesis has been hampered by the lack of an entirely plasmid-based reverse genetics system. in this study, we describe the recovery of recombinant rvs entirely from cloned cdnas. the strategy requires coexpression of a small transmembrane protein that accelerates cell-to-cell fusion and vaccinia vi ...201728137864
online size-exclusion and ion-exchange chromatography on a saxs beamline.biological small angle x-ray scattering (biosaxs) is a powerful technique in molecular and structural biology used to determine solution structure, particle size and shape, and surface-to-volume ratio of macromolecules. the technique is applicable to a very wide variety of solution conditions spanning a broad range of concentrations, ph values, ionic strengths, temperatures, additives, etc., but the sample is required to be monodisperse. this caveat led to the implementation of liquid chromatogr ...201728117806
detection of vaccinia virus in urban domestic cats, brazil.we investigated possible vaccinia virus (vacv) in urban house cats in brazil. serum samples from 6 cats were positive for vacv by pcr, indicating likely vacv circulation among house cats in urban areas of brazil. this finding highlights the importance of epidemiologic surveillance to avoid outbreaks among urban human populations.201728098542
coherent brightfield microscopy provides the spatiotemporal resolution to study early stage viral infection in live cells.viral infection starts with a virus particle landing on a cell surface followed by penetration of the plasma membrane. due to the difficulty of measuring the rapid motion of small-sized virus particles on the membrane, little is known about how a virus particle reaches an endocytic site after landing at a random location. here, we use coherent brightfield (cobri) microscopy to investigate early stage viral infection with ultrahigh spatiotemporal resolution. by detecting intrinsic scattered light ...201728067508
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