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ntcp and beyond: opening the door to unveil hepatitis b virus entry.chronic hepatitis b virus (hbv) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. given that current anti-hbv drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-hbv agents is urgently needed. the viral entry process is generally an attractive target implicated in antiviral strategies. using primary cells from humans ...201424557582
bats carry pathogenic hepadnaviruses antigenically related to hepatitis b virus and capable of infecting human hepatocytes.the hepatitis b virus (hbv), family hepadnaviridae, is one of most relevant human pathogens. hbv origins are enigmatic, and no zoonotic reservoirs are known. here, we screened 3,080 specimens from 54 bat species representing 11 bat families for hepadnaviral dna. ten specimens (0.3%) from panama and gabon yielded unique hepadnaviruses in coancestral relation to hbv. full genome sequencing allowed classification as three putative orthohepadnavirus species based on genome lengths (3,149-3,377 nt), ...201324043818
unraveling the complexity of hepatitis b virus: from molecular understanding to therapeutic strategy in 50 years.hepatitis b virus (hbv) is a well-known hepadnavirus with a double-stranded circular dna genome. although hbv was first described approximately 50 years ago, the precise mechanisms of hbv infection and effective therapeutic strategies remain unclear. here, we focus on summarizing the complicated mechanisms of hbv replication and infection, as well as genomic factors and epigenetic regulation. additionally, we discuss in vivo models of hbv, as well as diagnosis, prevention and therapeutic drugs f ...201323819994
combination of dna prime--adenovirus boost immunization with entecavir elicits sustained control of chronic hepatitis b in the woodchuck model.a potent therapeutic t-cell vaccine may be an alternative treatment of chronic hepatitis b virus (hbv) infection. previously, we developed a dna prime-adenovirus (adv) boost vaccination protocol that could elicit strong and specific cd8+ t-cell responses to woodchuck hepatitis virus (whv) core antigen (whcag) in mice. in the present study, we first examined whether this new prime-boost immunization could induce whcag-specific t-cell responses and effectively control whv replication in the whv-tr ...201323785279
persistent human hepatitis b virus infection in cynomolgus monkeys: a novel animal model in the search for a cure? 201323775673
occult hepatitis b virus infection in chacma baboons, south africa.during previous studies of susceptibility to hepatitis b virus (hbv) infection, hbv dna was detected in 2/6 wild-caught baboons. in the present study, hbv dna was amplified from 15/69 wild-caught baboons. all animals were negative for hbv surface antigen and antibody against hbv core antigen. liver tissue from 1 baboon was immunohistochemically negative for hbv surface antigen but positive for hbv core antigen. the complete hbv genome of an isolate from this liver clustered with subgenotype a2. ...201323631817
expression of matrix metalloproteinases and their inhibitors in the woodchuck model of hepatocellular carcinoma.matrix metalloproteinases (mmps) play a central role in tumor invasion and metastasis. increased expression of mmps occurs during development of hepatocellular carcinoma (hcc) in humans following infection with hepatitis b virus (hbv). woodchucks are used as an animal model for hepadnavirus-induced hcc. all woodchucks infected chronically with woodchuck hepatitis virus (whv), a virus that is closely related to hbv, develop hcc. in the present study mmps and related molecules were investigated in ...201323595580
novel recombinant hepatitis b virus vectors efficiently deliver protein and rna encoding genes into primary hepatocytes.hepatitis b virus (hbv) has extremely restricted host and hepatocyte tropism. hbv-based vectors could form the basis of novel therapies for chronic hepatitis b and other liver diseases and would also be invaluable for the study of hbv infection. previous attempts at developing hbv-based vectors encountered low yields of recombinant viruses and/or lack of sufficient infectivity/cargo gene expression in primary hepatocytes, which hampered follow-up applications. in this work, we constructed a nove ...201323552416
discovery of naturally occurring transmissible chronic hepatitis b virus infection among macaca fascicularis from mauritius island.despite a high prevalence of hepatitis b virus (hbv) infection in endangered apes, no hbv infection has been reported in small, old-world monkeys. in search for a small, nonhuman primate model, we investigated the prevalence of hbv infection in 260 macaque (cercopithecidae) sera of various geographical origins (i.e., morocco, mauritius island, and asia). hbv-positive markers were detected in cynomolgus macaques (macaca fascicularis) from mauritius island only, and, remarkably, hbv dna was positi ...201323536484
deregulation of epigenetic mechanisms by the hepatitis b virus x protein in hepatocarcinogenesis.this review focuses on the significance of deregulation of epigenetic mechanisms by the hepatitis b virus (hbv) x protein in hepatocarcinogenesis and hbv replication. epigenetic mechanisms, dna methylation, and specific histone modifications, e.g., trimethylation of h3 on lysine-27 or lysine-4, maintain 'cellular memory' by silencing expression of lineage-inducing factors in stem cells and conversely, of pluripotency factors in differentiated cells. the x protein has been reported to induce expr ...201323507839
avihepadnavirus diversity in parrots is comparable to that found amongst all other avian species.avihepadnaviruses have previously been isolated from various species of duck, goose, stork, heron and crane. recently the first parrot avihepadnavirus was isolated from a ring-necked parakeet in poland. in this study, 41 psittacine liver samples archived in poland over the last nine years were tested for presence of parrot hepatitis b virus (phbv). we cloned and sequenced phbv isolates from 18 birds including a crimson rosella, an african grey parrot and sixteen ring-necked parakeets. phbv isola ...201323411008
preclinical evaluation of a two-dose vaccination schedule of recombinant hansenula polymorpha hepatitis b vaccine in animals.the current 3-dose regimen of hepatitis b vaccination for infants requiring over 6 mo period may pose the poor rate of compliance and later protection from hepatitis b virus (hbv) infection. this preclinical study is to investigate the feasibility of reducing the number of doses of hepatitis b (hb) vaccine.201323370192
molecular characterization of woodchuck cd4 (wcd4) and production of a depletion monoclonal antibody against wcd4.cd4 t cells play an important role in the immune response against hepatitis b virus (hbv) infection. woodchucks represent an excellent animal model to study hbv infection. in this study, we characterized the cdna sequence of woodchuck cd4 (wcd4). the deduced wcd4 protein has four extracellular immunoglobulin-like domains comparable to the other mammalian cd4 molecules. the important extracellular cysteine residues and the intracellular tyrosine protein kinase-binding site of wcd4 are also conser ...201323685260
molecular determinants of hepatitis b and d virus entry restriction in mouse sodium taurocholate cotransporting polypeptide.human hepatitis b virus (hbv) and its satellite virus, hepatitis d virus (hdv), primarily infect humans, chimpanzees, or tree shrews (tupaia belangeri). viral infections in other species are known to be mainly restricted at the entry level since viral replication can be achieved in the cells by transfection of the viral genome. sodium taurocholate cotransporting polypeptide (ntcp) is a functional receptor for hbv and hdv, and amino acids 157 to 165 of ntcp are critical for viral entry and likely ...201323678176
molecular biology of the hepatitis b virus for clinicians.hepatitis b virus (hbv) infection is one of the major global health problems, especially in economically under-developed or developing countries. hbv infection can lead to a number of clinical outcomes including chronic infection, cirrhosis and liver cancer. it ranks among the top 10 causes of death, being responsible for around 1 million deaths every year. despite the availability of a highly efficient vaccine and potent antiviral agents, hbv infection still remains a significant clinical probl ...201225755457
[study on antibody response to revaccination of hepatitis b vaccine among firstly low-response adults].to evaluate and compare the antibody to hepatitis b virus (hbv) surface antigen (anti-hbs) response and the influent factors of revaccination of 4 kinds of hepatitis b vaccine (hepb) among firstly low-response adults.201223157885
repeated exposure to trace amounts of woodchuck hepadnavirus induces molecularly evident infection and virus-specific t cell response in the absence of serological infection markers and hepatitis.exposure to multiple small doses of hepatitis b virus (hbv) is a frequent occurrence in high-risk groups, including close relatives of infected individuals, primary care givers, and intravenous drug users. it remains uncertain whether such repeated contact may culminate in a symptomatic infection coinciding with hepatitis in individuals not immunoprotected. in this study, we evaluated consequences of multiple exposures to small, liver-nonpathogenic amounts of infectious hepadnavirus in the woodc ...201323135718
perspectives for a vaccine against hepatitis delta virus.hepatitis delta virus (hdv) causes severe hepatitis in carriers of hepatitis b virus (hbv). in ~90% of patients, hdv persists together with hbv and causes early development of cirrhosis and liver carcinoma. worldwide ~15 million people are coinfected with hbv-hdv. specific defects in the immune response causing persistence of the virus have not been identified. several approaches to develop a vaccine to prevent superinfection in the preclinical model of the woodchuck have failed. recent findings ...201222932974
experimental chronic hepatitis b infection of neonatal tree shrews (tupaia belangeri chinensis): a model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans.hepatitis b virus (hbv) infection continues to be an escalating global health problem. feasible and effective animal models for hbv infection are the prerequisite for developing novel therapies for this disease. the tree shrew (tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. whether tree shrews could be chronically infected with hbv in vivo has been controversial for decades. most published research has been repor ...201222913805
recombinant semliki forest virus vectors encoding hepatitis b virus small surface and pre-s1 antigens induce broadly reactive neutralizing antibodies.most hepatitis b virus (hbv) vaccines consist of viral small surface (s) protein subtype adw2 expressed in yeast cells. in spite of good efficacy, hbv-genotype and subtype differences, escape mutants and insufficient th1 activation remain potential problems. to address these problems, we generated recombinant semliki forest virus (rsfv) vectors encoding s protein, subtype adw2 or ayw2, or a fragment of the large surface protein, amino acids 1-48 of the pre-s1 domain, fused to s (pre-s1.1-48/s). ...201222863271
identification of an intrahepatic transcriptional signature associated with self-limiting infection in the woodchuck model of hepatitis b.the woodchuck model of hepatitis b virus (hbv) infection displays many characteristics of human infection and has particular value for characterizing the host immune responses during the development of chronic infection. using the newly developed custom woodchuck microarray platform, we compared the intrahepatic transcriptional profiles of neonatal woodchucks with self-limiting woodchuck hepatitis virus (whv) infection to those woodchucks progressing to persistent whv infection. this revealed th ...201322806943
molecular characterization of woodchuck interleukin-10 receptor and enhanced function of specific t cells from chronically infected woodchucks following its blockade.interleukin 10 (il-10) is a pleiotropic cytokine acting on a variety of immune cells through the cell surface receptor (il-10r). it has been suggested to resuscitate antiviral immunity by interfering with il-10/il-10r pathway. the woodchuck model infected by woodchuck hepatitis virus (whv) represents an informative animal model to study hepatitis b virus (hbv) infection. in this study, the woodchuck il-10r (wil-10r) was molecularly cloned and characterized, showing high similarity of its nucleot ...201222784930
hepatitis b virus x protein stimulates gene expression selectively from extrachromosomal dna templates.chronic hepatitis b virus (hbv) infection is a major risk factor for liver cancer development. hbv encodes the hepatitis b virus x (hbx) protein that promotes transcription of the viral episomal dna genome by the host cell rna polymerase ii. here we provide evidence that hbx accomplishes this task by a conserved and unusual mechanism. thus, hbx strongly stimulates expression of transiently transfected reporter constructs, regardless of the enhancer and promoter sequences. this activity invariabl ...201222744635
dna prime-adenovirus boost immunization induces a vigorous and multifunctional t-cell response against hepadnaviral proteins in the mouse and woodchuck model.induction of hepatitis b virus (hbv)-specific cytotoxic t cells by therapeutic immunization may be a strategy to treat chronic hepatitis b. in the hbv animal model, woodchucks, the application of dna vaccine expressing woodchuck hepatitis virus (whv) core antigen (whcag) in combination with antivirals led to the prolonged control of viral replication. however, it became clear that the use of more potent vaccines is required to overcome whv persistence. therefore, we asked whether stronger and mo ...201222718818
molecular characterization of the type i ifn receptor in two woodchuck species and detection of its expression in liver samples from woodchucks infected with woodchuck hepatitis virus (whv).type i interferons (ifn-α/β) serve as the first line of defense against viral infection and share the same type i ifn receptor (ifnar) complex, which is composed of ifnar1 and -2. the eastern woodchuck (marmota monax) and chinese woodchuck (marmota himalayana) are suitable for studying hepatitis b virus (hbv) infection. here, the complete or partial sequences of the ifnars of both species were obtained and analyzed. small interference rnas targeting wifnar1 and -2 specifically down-regulated the ...201222705153
human hepatitis b virus production in avian cells is characterized by enhanced rna splicing and the presence of capsids containing shortened genomes.experimental studies on hepatitis b virus (hbv) replication are commonly done with human hepatoma cells to reflect the natural species and tissue tropism of the virus. however, hbv can also replicate, upon transfection of virus coding plasmids, in cells of other species. in such cross-species transfection experiments with chicken lmh hepatoma cells, we previously observed the formation of hbv genomes with aberrant electrophoretic mobility, in addition to the those dna species commonly seen in hu ...201222624002
role of toll-like receptor 2 in the immune response against hepadnaviral infection.the toll-like receptor 2 (tlr2) has recently been recognized to play an important role in the pathogenesis of chronic hepatitis b virus (hbv) infection. in the present study, we examined the role of tlr2 in hepadnaviral infection in hepatoma cell lines and the woodchuck model.201222617154
entecavir treatment of chronic hepatitis d.hepatitis d virus (hdv) requires hepatitis b surface antigen (hbsag) to propagate infection and cause disease. entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis b virus (hbv) cccdna and woodchuck surface antigen. the aim of this study was to investigate the efficacy of entecavir in chronic hepatitis d (chd).201222573857
subset of suz12/prc2 target genes is activated during hepatitis b virus replication and liver carcinogenesis associated with hbv x protein.chronic hepatitis b virus (hbv) infection is a major risk factor for developing liver cancer, and the hbv x protein (px) has been implicated as a cofactor in hepatocyte transformation. we have shown that hbv replication as well as in vitro transformation by px are associated with induction of the mitotic polo-like kinase 1 (plk1) and down-regulation of the chromatin remodeling components suz12 and znf198. herein, we demonstrate the same inverse relationship between plk1 and suz12/znf198 in liver ...201222505317
species association of hepatitis b virus (hbv) in non-human apes; evidence for recombination between gorilla and chimpanzee variants.hepatitis b virus (hbv) infections are widely distributed in humans, infecting approximately one third of the world's population. hbv variants have also been detected and genetically characterised from old world apes; gorilla gorilla (gorilla), pan troglodytes (chimpanzee), pongo pygmaeus (orang-utan), nomascus nastusus and hylobates pileatus (gibbons) and from the new world monkey, lagothrix lagotricha (woolly monkey). to investigate species-specificity and potential for cross species transmiss ...201222432021
transcriptomic analysis of the woodchuck model of chronic hepatitis b.the eastern woodchuck (marmota monax) is naturally infected with woodchuck hepatitis virus (whv), a hepadnavirus closely related to the human hepatitis b virus (hbv). the woodchuck is used as an animal model for studying chronic hepatitis b (chb) and hbv-associated hepatocellular carcinoma (hcc) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. to address this major limitation of the model, we report here the sequencing, assembly, and annotation ...201222431061
prime/boost immunization with dna and adenoviral vectors protects from hepatitis d virus (hdv) infection after simultaneous infection with hdv and woodchuck hepatitis virus.hepatitis d virus (hdv) superinfection of hepatitis b virus (hbv) carriers causes severe liver disease and a high rate of chronicity. therefore, a vaccine protecting hbv carriers from hdv superinfection is needed. to protect from hdv infection an induction of virus-specific t cells is required, as antibodies to the two proteins of hdv, p24 and p27, do not neutralize the hbv-derived envelope of hdv. in mice, hdv-specific cd8(+) and cd4(+) t cell responses were induced by a dna vaccine expressing ...201323637419
[factors influencing long-term hepatitis b virus infection of the tree shrew (tupaia belangeri chinensis) as an in vivo model of chronic hepatitis b].to determine the methods for establishing an in vivo model of long-term hepatitis b virus (hbv) infection in the chinese tree shrew (tupaia belangeri chinensis).201223207228
modulation of regulatory t-cell activity in combination with interleukin-12 increases hepatic tolerogenicity in woodchucks with chronic hepatitis b.regulatory t cells (treg) play a critical role in the modulation of immune responses to viral antigens in chronic viral hepatitis. woodchucks (marmota monax) infected with the woodchuck hepatitis virus (whv) represent the best animal model for chronic hepatitis b virus (hbv) infection. examination of intrahepatic and peripheral treg in uninfected and whv chronically infected woodchucks showed a significant increase of intrahepatic treg numbers in chronically infected animals, whereas no differen ...201222334260
long-term efficacy of 10-12 years after being immunized with chinese hamster ovary cell derived hepatitis b vaccine in chinese rural communities.to evaluate the long-term efficacy of chinese hamster ovary (cho) cell derived hepatitis b vaccine in country community in china.201222296954
hepatitis b virus hepatotropism is mediated by specific receptor recognition in the liver and not restricted to susceptible hosts.the human hepatitis b virus (hbv) causes acute and chronic infections in humans and chimpanzees. hbv infects its hosts at minimal inoculation doses and replicates exclusively in hepatocytes. the viral determinants for the pronounced species specificity and the high efficacy to address hepatocytes in vivo are unknown. previous findings showed that n-terminally myristoylated peptides constituting a receptor binding domain of the hbv large envelope (l)-protein block hbv entry in vitro and in vivo. ...201323292963
ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis b virus.overexpression of squamous cell carcinoma antigen 1 (scca1) in hepatitis g2 (hepg2) and chinese hamster ovary cells can increase hepatitis b virus (hbv) binding capacity by interacting with the pres1 domain of the hbv surface antigen. however, the magnitude of increase in binding capacity was higher by several orders in the former, indicating the existence of additional factor(s) produced by hepg2 cells, which facilitates hbv attachment. ferritin light chain (ftl) was identified as the sole high ...201222359459
evaluation of heterologous vaginal shiv sf162p4 infection following vaccination with a polyvalent clade b virus-like particle vaccine.the vast diversity of hiv-1 infections has greatly impeded the development of a successful hiv-1/aids vaccine. previous vaccine work has demonstrated limited levels of protection against shiv/siv infection, but protection was observed only when the challenge virus was directly matched to the vaccine strain. as it is likely impossible to directly match the vaccine strain to all infecting strains in nature, it is necessary to develop an hiv-1 vaccine that can protect against a heterologous viral c ...201222214267
recombinant subgroup b human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats.human respiratory syncytial virus (hrsv) is the most important viral cause of severe respiratory tract disease in infants. two subgroups (a and b) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. existing in vitro and in vivo models of hrsv focus almost exclusively on subgroup a viruses. here, a recombinant (r) subgroup b virus (rhrsv(b05)) was generated based on a consensus genome sequence obtained directly from an unpas ...201525540371
development of high-yield influenza b virus vaccine viruses.the burden of human infections with influenza a and b viruses is substantial, and the impact of influenza b virus infections can exceed that of influenza a virus infections in some seasons. over the past few decades, viruses of two influenza b virus lineages (victoria and yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the world health organization. influenza b virus vaccines for humans have been available for more than half a c ...201627930325
recombinant production and characterization of human anti-influenza virus monoclonal antibodies identified from hybridomas fused with human lymphocytes.in previous studies, hybridomas producing human immunoglobulin g, the antibodies 5e4 and 5a7 against influenza a and b virus were established using a novel human lymphocyte fusion partner, spymeg. in the present study, we succeeded in achieving the recombinant production and secretion of 5e4 and 5a7 in chinese hamster ovary cells. our n-glycan analysis by intact-mass detection and liquid chromatography mass spectrometry showed that recombinant 5e4 and 5a7 have one n-glycan and the typical mammal ...201627464991
transmission of influenza b viruses in the guinea pig.epidemic influenza is typically caused by infection with viruses of the a and b types and can result in substantial morbidity and mortality during a given season. here we demonstrate that influenza b viruses can replicate in the upper respiratory tract of the guinea pig and that viruses of the two main lineages can be transmitted with 100% efficiency between inoculated and naïve animals in both contact and noncontact models. our results also indicate that, like in the case for influenza a virus, ...201222301149
macacine herpesvirus 1 in long-tailed macaques, malaysia, 2009-2011.macacine herpesvirus 1 (mahv1; b virus) naturally infects macaques (macaca spp.) and can cause fatal encephalitis in humans. in peninsular malaysia, wild macaques are abundant, and translocation is used to mitigate human-macaque conflict. most adult macaques are infected with mahv1, although the risk for transmission to persons who handle them during capture and translocation is unknown. we investigated mahv1 shedding among 392 long-tailed macaques (m. fascicularis) after capture and translocati ...201526080081
genome sequence of a pathogenic isolate of monkey b virus (species macacine herpesvirus 1).the only genome sequence for monkey b virus (bv; species macacine herpesvirus 1) is that of an attenuated vaccine strain originally isolated from a rhesus monkey (bvrh). here we report the genome sequence of a virulent bv strain isolated from a cynomolgus macaque (bvcy). the overall genome organization is the same, although sequence differences exist. the greatest sequence divergence is located in non-coding areas of the long and short repeat regions. like bvrh, bvcy has duplicated ori elements ...201424903602
multiple antibody targets on herpes b glycoproteins b and d identified by screening sera of infected rhesus macaques with peptide microarrays.herpes b virus (or herpesvirus simiae or macacine herpesvirus 1) is endemic in many populations of macaques, both in the wild and in captivity. the virus elicits only mild clinical symptoms (if any) in monkeys, but can be transmitted by various routes, most commonly via bites, to humans where it causes viral encephalitis with a high mortality rate. hence, herpes b constitutes a considerable occupational hazard for animal caretakers, veterinarians and laboratory personnel. efforts are therefore b ...201424497986
herpes b virus, macacine herpesvirus 1, breaks simplex virus tradition via major histocompatibility complex class i expression in cells from human and macaque hosts.b virus of the family herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. downregulation of major histocompatibility complex (mhc) class i in order to evade cd8(+) t-cell activation is characteristic of most herpesviruses. here we examined the cell surface presence and total protein expression of mhc class i molecules in b virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are ...201222973043
hepatitis delta virus infects the cells of hepadnavirus-induced hepatocellular carcinoma in woodchucks.hepatitis delta virus (hdv) is a natural subviral agent of human hepatitis b virus (hbv). hdv enhances liver damage during concomitant infection with hbv. the molecular pathogenesis of hdv infection remains poorly understood. to advance our understanding of the relationship between hdv infection and liver cancer, it was determined whether hdv could infect in vivo the cells of hepadnavirus-induced hepatocellular carcinoma (hcc). woodchucks (marmota monax) that were chronically infected with hbv-r ...201222334419
the woodchuck hepatitis b virus infection model for the evaluation of hbv therapies and vaccine therapies.studies focused on the understanding of the molecular mechanisms involved in recovery or progression to chronicity of hbv may take advantage of natural and experimental models that mimic its properties. this is also of relevance for associated diseases such as cirrhosis and hepatocellulocarcinoma. the eastern woodchuck (marmota monax) infected by the hepadnavirus woodchuck hepatitis b virus (whv) has been applied as a predictive model to support development of new hbv vaccines, antivirals, immun ...201022822718
animal models for influenza virus pathogenesis, transmission, and immunology.in humans, infection with an influenza a or b virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. however, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. disease severity depends upon the virulence of the influenza virus strain and the immune competence and pre ...201424709389
rationally designed influenza virus vaccines that are antigenically stable during growth in eggs.influenza virus vaccine production is currently limited by the ability to grow circulating human strains in chicken eggs or in cell culture. to facilitate cost-effective growth, vaccine strains are serially passaged under production conditions, which frequently results in mutations of the major antigenic protein, the viral hemagglutinin (ha). human vaccination with an antigenically drifted strain is known to contribute to poor vaccine efficacy. to address this problem, we developed a replication ...201728588131
marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques.marburg virus (marv), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (nhps) with a mortality rate of up to 90%. currently, there is no effective treatment or approved vaccine for marv for human use to control disease outbreak and spread. virus-like particles (vlps), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus ( ...201728402024
herpes b virus replication and viral lesions in the liver of a cynomolgus macaque which died from severe disease with rapid onset.herpes b virus (bv, macacine alphaherpesvirus 1) infects macaques asymptomatically, with rare exceptions, but can cause fatal encephalitis in humans. here, we report disseminated bv infection in a cynomolgus macaque that had died within 12 hour after the onset of unspecific symptoms. multifocal lesions surrounded by viral antigen were detected in liver while other organs remained inconspicuous, indicating that the liver is a major target. moreover, high copy numbers of viral dna were found in fe ...201728439900
efficient and inducible production of human interleukin 6 in chinese hamster ovary cells using a novel expression system.high level and inducible production of human interleukin 6 (hil-6) was achieved using a novel expression system in chinese hamster ovary (cho) cells. in this system, the transcription of hil-6 gene under the control of phcmv*-1 promoter composed of tetracycline operator sequences and a minimal promoter is activated by a chimeric transactivator (tta) composed of tetracycline repressor and transactivating domain of vp16 protein of herpes simplex virus. the transcription of tta gene, which is also ...199722358879
genome sequence variation among isolates of monkey b virus (macacine alphaherpesvirus 1) from captive macaques.complete genome sequences of 19 strains of monkey b virus (macacine alphaherpesvirus 1; bv) isolated from several macaque species were determined. a low level of sequence variation was present among bv isolates from rhesus macaques. most variation among bv strains isolated from rhesus macaques was located in regions of repetitive or quasi-repetitive sequence. variation in coding sequences (polypeptides and mirnas) was minor compared to regions of non-coding sequences. non-coding sequences in the ...201728494342
recombinant vaccinia vector-based vaccine (tiantan) boosting a novel hbv subunit vaccine induced more robust and lasting immunity in rhesus macaques.this study explored several prime-boost strategies in rhesus macaques using various novel hepatitis b virus (hbv) vaccines that showed promise as prophylactic and therapeutic approaches in our previous study using in a mouse model. the tested vaccines included an hbv particle subunit (hbss1) vaccine and the recombinant vaccinia (rvjss1) or adenoviral (radss1) vector-based vaccines containing s (1-223aa) and pres1 (21-47aa). the strength and maintenance of humoral activity (igg and neutralizing a ...201728487055
a polyvalent clade b virus-like particle hiv vaccine combined with partially protective oral preexposure prophylaxis prevents simian-human immunodeficiency virus infection in macaques and primes for virus-amplified immunity.vaccination and preexposure prophylaxis (prep) with antiretrovirals have shown only partial protection from hiv-1 infection in human trials. oral truvada (emtricitabine/tenofovir disoproxil fumarate) is fda approved as prep but partial adherence reduces efficacy. if combined as biomedical preventions (cbp), an hiv vaccine could protect when prep adherence is low and prep could prevent vaccine breakthroughs. the efficacy of combining oral prep with an hiv vaccine has not been evaluated in humans. ...201424914761
[epidemiological survey of a captive chinese rhesus macaque breeding colony in yunnan for srv, stlv and bv].nonhuman primates are critical resources for biomedical research. rhesus macaque is a popularly used laboratory nonhuman primate that share many characteristics with humans. however, rhesus macaques are the natural host of two exogenous retroviruses, srv (simian type d retrovirus) and stlv (simian t lymphotropic virus). srv and stlv may introduce potentially significant confounding factors into the study of aids model. moreover, b virus (ceropithecine herpesvirus 1) is likely to harm not only rh ...201222345008
pathology in practice. b virus infection in a rhesus macaque. 201323600779
identification of unique b virus (macacine herpesvirus 1) epitopes of zoonotic and macaque isolates using monoclonal antibodies.our overall aim is to develop epitope-based assays for accurate differential diagnosis of b virus zoonotic infections in humans. antibodies to cross-reacting epitopes on human-simplexviruses continue to confound the interpretation of current assays where abundant antibodies exist from previous infections with hsv types 1 and 2. to find b virus-specific epitopes we cloned ten monoclonal antibodies (mabs) from the hybridomas we produced. our unique collection of rare human sera from symptomatic an ...201728783746
interferon-β response is impaired by hepatitis b virus infection in tupaia belangeri.to date, the chimpanzee has been used as the natural infection model for hepatitis b virus (hbv). however, as this model is very costly and difficult to use because of ethical and animal welfare issues, we aimed to establish the tupaia (tupaia belangeri) as a new model for hbv infection and characterized its intrahepatic innate immune response upon hbv infection. first, we compared the propagation of hbv genotypes a2 and c in vivo in tupaia hepatocytes. at 8-10days post infection (dpi), the leve ...201728551415
biological effects of bone marrow mesenchymal stem cells on hepatitis b virus in vitro.the aim of the present study was to explore the effects of co‑culturing bone marrow‑derived mesenchymal stem cells (bm-mscs) cultured with hepatitis b virus (hbv)‑infected lymphocytes in vitro. bm‑mscs and lymphocytes from brown norway rats were obtained from the bone marrow and spleen, respectively. rats were divided into the following five experimental groups: group 1, splenic lymphocytes (slcs); group 2, hepg2.2.15 cells; group 3, bm‑mscs + hepg2.2.15 cells; group 4, slcs + hepg2.2.15 cells; ...201728447750
is it possible to develop cancer vaccines to neoantigens, what are the major challenges, and how can these be overcome? neoantigens: nothing new in spite of the name.the term "neoantigen," as applied to molecules newly expressed on tumor cells, has a long history. the groundbreaking discovery of a cancer causing virus in chickens by rous over 100 years ago, followed by discoveries of other tumor-causing viruses in animals, suggested a viral etiology of human cancers. the search for other oncogenic viruses in the 1960s and 1970s resulted in the discoveries of epstein-barr virus (ebv), hepatitis b virus (hbv), and human papilloma virus (hpv), and continues unt ...201729254980
tumour virus epidemiology.a viral etiology of cancer was first demonstrated in 1911 by peyton rous who injected cell-free filtrate from a chicken sarcoma into healthy chickens and found it induced a tumour. since the discovery over 50 years ago of the epstein-barr virus as the cause of burkitt lymphoma, seven other human viruses or groups of viruses-hepatitis b virus, hepatitis c virus, human immunodeficiency virus type 1, some human papillomaviruses, human t-cell lymphotropic virus type 1, kaposi sarcoma-associated herp ...201728893933
construction of a hepatitis b virus neutralizing chimeric monoclonal antibody recognizing escape mutants of the viral surface antigen (hbsag).hepatitis b virus (hbv) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. over 248 million patients are currently suffering from chronic hbv infection worldwide and annual mortality rate of this infection is 686000. the "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis b surface antigen (hbsag), and antibodies against this region can neutralize the virus and are protective against all su ...201728641998
initial sites of hepadnavirus integration into host genome in human hepatocytes and in the woodchuck model of hepatitis b-associated hepatocellular carcinoma.hepatitis b virus (hbv) and the closely related woodchuck hepatitis virus (whv) are potent carcinogens that trigger development of primary hepatocellular carcinoma (hcc). the initial sites of hepadnavirus-host genome integration, their diversity and kinetics of formation can be central to virus persistence and the initiation and progression of hcc. to recognize the nature of the very early virus-host interactions, we explored de novo infection of human hepatocyte-like heparg cells with authentic ...201728414318
syrian hamster as an animal model for the study of human influenza virus infection.ferrets and mice are frequently used as animal models for influenza research. however, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza a or b viruses. therefore, prior adaptation of human viruses is required for their use in mice. in addition, there are no mouse-adapted variants of the recent h3n2 viruses, because these viruses do not replicate well in mice. in this study, we investigated the susceptibilit ...201729212926
macacine herpesvirus 1 antibody prevalence and dna shedding among invasive rhesus macaques, silver springs state park, florida, usa.we compiled records on macacine herpesvirus 1 (mchv-1) seroprevalence and, during 2015-2016, collected saliva and fecal samples from the free-ranging rhesus macaques of silver springs state park, a popular public park in central florida, usa, to determine viral dna shedding and perform sequencing. phylogenetic analysis of the us5 and us5-us6 intragenic sequence from free-ranging and laboratory mchv-1 variants did not reveal genomic differences. in animals captured during 2000-2012, average annua ...201829350146
immunization with live human rhinovirus (hrv) 16 induces protection in cotton rats against hrv14 infection.human rhinoviruses (hrvs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against hrvs are available to prevent or mitigate hrv infection. there are more than 150 antigenically heterogeneous hrv serotypes, with ∼90 hrvs belonging to major group species a and b. development of small animal models that are susceptible to infection with major group hrvs would be beneficial for vaccine research. previously, we showed that the cotton rat (sigmodon hispidus) ...201728912760
toll-like receptor 7 agonist gs-9620 induces prolonged inhibition of hbv via a type i interferon-dependent mechanism.gs-9620, an oral agonist of toll-like receptor 7 (tlr7), is in clinical development for the treatment of chronic hepatitis b (chb). gs-9620 was previously shown to induce prolonged suppression of serum viral dna and antigens in the woodchuck and chimpanzee models of chb. here we investigated the molecular mechanisms that contribute to the antiviral response to gs-9620 using in vitro models of hepatitis b virus (hbv) infection.201729247725
anti-hbv response to toll-like receptor 7 agonist gs-9620 is associated with intrahepatic aggregates of t cells and b cells.gs-9620, an oral agonist of toll-like receptor 7 (tlr7), is in clinical development for the treatment of chronic hepatitis b (chb). gs-9620 was previously shown to induced prolonged suppression of serum viral dna and antigens in the chimpanzee and woodchuck models of chb. here we investigated the immunomodulatory mechanisms underlying these antiviral effects.201729247724
tlr7 agonist increases responses of hepatitis b virus-specific t cells and natural killer cells in patients with chronic hepatitis b treated with nucleos(t)ide analogues.the oral toll-like receptor (tlr) 7 agonist gs-9620 has antiviral effects in woodchuck and chimpanzee models of chronic hepatitis b virus (hbv) infection. we investigated, in a clinical trial, the capacity of this agent to reconstitute protective immunity in patients with chronic hbv infection.201829378197
animal models for the study of hepatitis b virus infection.even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis b virus (hbv) worldwide. current antiviral therapies, including interferon and nucleot(s)ide analogues, rarely cure chronic hepatitis b. animal models are very crucial for understanding the pathogenesis of chronic hepatitis b and developing new therapeutic drugs or strategies. hbv can only infect humans and chimpanzees, with the use of chimpanzees in hbv research strongly restricted. thus, mos ...201829511142
mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent proechimys semispinosus.hepatitis delta virus (hdv) is a human hepatitis-causing rna virus, unrelated to any other taxonomic group of rna viruses. its occurrence as a satellite virus of hepatitis b virus (hbv) is a singular case in animal virology for which no consensus evolutionary explanation exists. here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species proechimys semispinosus the rodent deltavirus is highly distinct, showing a common ancestor with a recent ...202032651267
detection of hepatitis b virus-like nucleotide sequences in liver samples from murine rodents and asian house shrews.in recent years, hepatitis b virus (hbv) has been detected in some species of animals. in this study, we found hbv-like nucleotide sequences in murine rodents and asian house shrews (suncus murinus) collected in china. a total of 801 animals were trapped. we found that 0.48% (3/624) of the murine rodents and 1.69% (3/177) of asian house shrews were positive for hbv-like dna. detection of hbv-like dna in brown rats (rattus norvegicus), rice-field rat (rattus losea), and asian house shrews indicat ...201931216240
intranasal vaccination with hbs and hbc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-hbs iga, and ifng response.hepatitis b virus (hbv) infection causes acute and chronic hepatitis, which is a major public health concern worldwide. immunization methods incorporating hepatitis b surface-small (hbs-s) antigen and hepatitis b core antigen (hbc) have been proposed as candidate therapeutic vaccines, but the elimination of existing hbv infection remains a challenge. to enhance the efficacy of hbs and hbc vaccination, we investigated hbs-large (hbs-l) as an immunogen, and carboxyl vinyl polymer (cvp) as an excip ...201931582218
construction of complete tupaia belangeri transcriptome database by whole-genome and comprehensive rna sequencing.the northern tree shrew (tupaia belangeri) possesses high potential as an animal model of human diseases and biology, given its genetic similarity to primates. although genetic information on the tree shrew has already been published, some of the entire coding sequences (cdss) of tree shrew genes remained incomplete, and the reliability of these cdss remained difficult to determine. to improve the determination of tree shrew cdss, we performed sequencing of the whole-genome, mrna, and total rna ...201931451757
the tree shrew is a promising model for the study of influenza b virus infection.influenza b virus is a main causative pathogen of annual influenza epidemics, however, research on influenza b virus in general lags behind that on influenza a viruses, one of the important reasons is studies on influenza b viruses in animal models are limited. here we investigated the tree shrew as a potential model for influenza b virus studies.201931174549
characterisation of the hepatitis b virus cross-species transmission pattern via na+/taurocholate co-transporting polypeptides from 11 new world and old world primate species.the hepatic na+/taurocholate co-transporting polypeptide (ntcp in man, ntcp in animals) is the high-affinity receptor for the hepatitis b (hbv) and hepatitis d (hdv) viruses. species barriers for human hbv/hdv within the order primates were previously attributed to ntcp sequence variations that disable virus-receptor interaction. however, only a limited number of primate ntcps have been analysed so far. in the present study, a total of 11 ntcps from apes, old and new world monkeys were cloned an ...201829912972
detection systems for antibody responses against herpes b virus.herpes b virus (bv) infection is highly prevalent among adult asian macaques and rarely causes severe disease in infected animals. in contrast, bv infection of humans can induce fatal encephalitis in the absence of treatment. therefore, the development of diagnostic tests for specific and sensitive detection of antibodies against bv is an important task. the cross-reactivity of antibodies against bv with related simplex viruses of other primates may afford an opportunity to obtain sensitive dete ...201732110687
seroprevalence of viral infections in captive rhesus and cynomolgus macaques.macaques serve as important animal models for biomedical research. viral infection of macaques can compromise animal health as well as the results of biomedical research, and infected animals constitute an occupational health risk. therefore, monitoring macaque colonies for viral infection is an important task. we used a commercial chip-based assay to analyze sera of 231 macaques for the presence of antibody responses against nine animal and human viruses. we report high seroprevalence of cytome ...201932110713
a unique b cell epitope-based particulate vaccine shows effective suppression of hepatitis b surface antigen in mice.this study aimed to develop a novel therapeutic vaccine based on a unique b cell epitope and investigate its therapeutic potential against chronic hepatitis b (chb) in animal models.202030926653
safety and efficacy of anti-pd-l1 therapy in the woodchuck model of hbv infection.immune clearance of hepatitis b virus (hbv) is characterized by broad and robust antiviral t cell responses, while virus-specific t cells in chronic hepatitis b (chb) are rare and exhibit immune exhaustion that includes programmed-death-1 (pd-1) expression on virus-specific t cells. thus, an immunotherapy able to expand and activate virus-specific t cells may have therapeutic benefit for chb patients. like hbv-infected patients, woodchucks infected with woodchuck hepatitis virus (whv) can have i ...201829444087
new avian hepadnavirus in palaeognathous bird, germany.in 2015, we identified an avian hepatitis b virus associated with hepatitis in a group of captive elegant-crested tinamous (eudromia elegans) in germany. the full-length genome of this virus shares <76% sequence identity with other avihepadnaviruses. the virus may therefore be considered a new extant avian hepadnavirus.201729148393
questioning the extreme neurovirulence of monkey b virus (macacine alphaherpesvirus 1).monkey b virus (macacine alphaherpesvirus 1; bv) occurs naturally in macaques of the genus macaca, which includes rhesus and long-tailed (cynomolgus) monkeys that are widely used in biomedical research. bv is closely related to the human herpes simplex viruses (hsv), and bv infections in its natural macaque host are quite similar to hsv infections in humans. zoonotic bv is extremely rare, having been diagnosed in only a handful of north american facilities with the last documented case occurring ...201829666644
effects of social reorganization on cellular immunity in male cynomolgus monkeys.exposure to acute stressors has been shown to impair cellular immunity in human beings and other animal species. comparatively little is known, however, about the effects of long-term stressors on immune function and how individual behavioral characteristics may mediate differences in immune function and clinical disease susceptibility. to determine the effects of social stress on cellular immunity and reactivation of a latent herpesvirus, 20 herpes b virus-positive male cynomolgus monkeys were ...199631918506
innovative hbv animal models based on the entry receptor ntcp.hepatitis b is a major global health problem, with an estimated 257 million chronically infected patients and almost 1 million deaths per year. the causative agent is hepatitis b virus (hbv), a small, enveloped, partially double-stranded dna virus. hbv has a strict species specificity, naturally infecting only humans and chimpanzees. sodium taurocholate co-transporting polypeptide (ntcp), a bile acid transporter expressed on hepatocytes, has been shown to be one of the key factors in hbv infecti ...202032751581
mhc-e-restricted cd8+ t cells target hepatitis b virus-infected human hepatocytes.currently 247 million people are living with chronic hepatitis b virus infection (chb), and the development of novel curative treatments is urgently needed. immunotherapy is an attractive approach to treat chb, yet therapeutic approaches to augment the endogenous hepatitis b virus (hbv)-specific t cell response in chb patients have demonstrated little success. in this study, we show that strain 68-1 rhesus macaque (rm) cmv vaccine vectors expressing hbv ags engender hbv-specific cd8+ t cells unc ...202032161099
feasibility of hepatitis b vaccination by microneedle patch: cellular and humoral immunity studies in rhesus macaques.this study evaluated dissolvable microneedle patch (dmnp) delivery of hepatitis b vaccine in rhesus macaques and provides evidence that dmnp delivery elicits seroprotective anti-hbs levels comparable with human seroprotection, potentially useful for hepatitis b birth dose vaccination in resource-constrained regions.201931408163
hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis b virus infection of macaques.hepatitis b virus (hbv) is a major global health concern, and the development of curative therapeutics is urgently needed. such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of hbv infection. here, we report that expression of the hbv entry receptor, human sodium-taurocholate cotransporting polypeptide (hntcp), on macaque primary hepatocytes facilitates hbv infection in vitro, where all replicative intermediates including covalently closed circular dna ...201729247188
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
divergent influenza-like viruses of amphibians and fish support an ancient evolutionary association.influenza viruses (family orthomyxoviridae) infect a variety of vertebrates, including birds, humans, and other mammals. recent metatranscriptomic studies have uncovered divergent influenza viruses in amphibians, fish and jawless vertebrates, suggesting that these viruses may be widely distributed. we sought to identify additional vertebrate influenza-like viruses through the analysis of publicly available rna sequencing data. accordingly, by data mining, we identified the complete coding segmen ...202032962015
antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development.the sexually transmitted infections (stis) caused by viruses including human t cell leukemia virus type-1 (htlv-1), human immunodeficiency virus-1 (hiv-1), human simplex virus-2 (hsv-2), hepatitis c virus (hcv), hepatitis b virus (hbv), and human papillomavirus (hpv) are major public health issues. these infections can cause cancer or result in long-term health problems. due to high prevalence of stis, a safe and effective vaccine is required to overcome these fatal viruses.202032838584
animal models for the study of human hepatitis b and d virus infection: new insights and progress.hepatitis b virus (hbv) is a member of the hepadnaviridae family and infects hepatocytes, leading to liver pathology in acutely and chronically infected individuals. co-infection with hepatitis d virus (hdv), which requires the surface proteins of hbv to replicate, can exacerbate this disease progression. thus, the >250 million people living with chronic hbv infection, including 13 million co-infected with hdv, would significantly benefit from an effective and affordable curative treatment. anim ...202032758525
genomic nucleotide-based distance analysis for delimiting old world monkey derived herpes simplex virus species.herpes simplex viruses form a genus within the alphaherpesvirus subfamily, with three identified viral species isolated from old world monkeys (owm); macacine alphaherpesvirus 1 (mchv-1; herpes b), cercopithecine alphaherpesvirus 2 (sa8), and papiine alphaherpesvirus 2 (pahv-2; herpes papio). herpes b is endemic to macaques, while pahv-2 and sa8 appear endemic to baboons. all three viruses are genetically and antigenically similar, with sa8 and pahv-2 thought to be avirulent in humans, while her ...202032590937
ati-2173, a novel liver-targeted non-chain-terminating nucleotide for hepatitis b virus cure regimens.ati-2173 is a novel liver-targeted molecule designed to deliver the 5'-monophosphate of clevudine for the treatment of chronic hepatitis b infection. unlike other nucleos(t)ides, the active clevudine-5'-triphosphate is a noncompetitive, non-chain-terminating inhibitor of hepatitis b virus (hbv) polymerase that delivers prolonged reduction of viremia in both a woodchuck hbv model and in humans for up to 6 months after cessation of treatment. however, long-term clevudine treatment was found to exh ...202032540975
antiviral properties of extracts of streptomyces sp. smu 03 isolated from the feces of elephas maximus.actinobacteria are historically and continued to be an important source for drug discovery. the annual epidemics and periodic pandemics of humans induced by influenza a virus (iav) prompted us to develop new effective antiviral drugs with different modes of action. an actinobacterium of streptomyces sp. smu 03 was identified from the feces of elephas maximus in yunnan province, china. by employing an h5n1 pseudo-typed virus drug screening system, the anti-iav effect of the dichloromethane extrac ...202032330578
genetic and molecular features for hepadnavirus and plague infections in the himalayan marmot.the himalayan marmot (marmota himalayana), a natural host and transmitter of plague, is also susceptible to the hepadnavirus infection. to reveal the genetic basis of the hepadnavirus susceptibility and the immune response to plague, we systematically characterized the features of immune genes in himalayan marmot with those of human and mouse. we found that the entire major histocompatibility complex region and the hepatitis b virus pathway genes of the himalayan marmot were conserved with those ...202032308030
innate and adaptive immunity associated with resolution of acute woodchuck hepatitis virus infection in adult woodchucks.viral and/or host factors that are directly responsible for the acute versus chronic outcome of hepatitis b virus (hbv) infection have not been identified yet. information on immune response during the early stages of hbv infection in humans is mainly derived from blood samples of patients with acute hepatitis b (ahb), which are usually obtained after the onset of clinical symptoms. features of intrahepatic immune response in these patients are less studied due to the difficulty of obtaining mul ...201931869393
a fosmid-based system for the generation of recombinant cercopithecine alphaherpesvirus 2 encoding reporter genes.the transmission of macacine alphaherpesvirus 1 (mchv-1) from macaques, the natural host, to humans causes encephalitis. in contrast, human infection with cercopithecine alphaherpesvirus 2 (cehv-2), a closely related alphaherpesvirus from african vervet monkeys and baboons, has not been reported and it is believed that cehv-2 is apathogenic in humans. the reasons for the differential neurovirulence of mchv-1 and cehv-2 have not been explored on a molecular level, in part due to the absence of sy ...201931694178
mucosal immunity against neuraminidase prevents influenza b virus transmission in guinea pigs.despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. however, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. importantly, antineuraminidase immunity was shown to be r ...201931113896
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