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autophagy in plasma cell ontogeny and malignancy.autophagy is a highly conserved pathway that recycles cytosolic material and organelles via lysosomal degradation. once simplistically viewed as a non-selective survival strategy in dire straits, autophagy has emerged as a tightly regulated process ensuring organelle function, proteome plasticity, cell differentiation and tissue homeostasis, with key roles in physiology and disease. selective target recognition, mediated by specific adapter proteins, enables autophagy to orchestrate highly speci ...201626984755
endogenously-expressed nh2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands.the circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria parasite stage capable of infecting humans. sporozoite invasion of mosquito salivary glands prior to transmission is likely mediated by a receptor/ligand-like interaction of the parasites with the target tissues, and the amino (nh2)-terminal portion of csp is involved in this interaction but not the tsr region on the carboxyl (c)-terminus. peptides based on the nh2-terminal domain could compete wi ...201626964736
filopodia and viruses: an analysis of membrane processes in entry mechanisms.filopodia are thin, actin rich bundles protruding from cell plasma membranes, serving physiological purposes, such as probing the environment and facilitating cell-to-cell adhesion. recent studies have highlighted that actively polymerized filopodial-protrusions are exploited during virus entry, trafficking, spread, and the development of clinical pathology of viral diseases. these observations have caused a surge in investigation of the key determinants of filopodial induction and their influen ...201627014223
pseudomonas aeruginosa activates pkc-alpha to invade middle ear epithelial cells.otitis media (om) is a group of complex inflammatory disorders affecting the middle ear which can be acute or chronic. chronic suppurative otitis media (csom) is a form of chronic om characterized by tympanic membrane perforation and discharge. despite the significant impact of csom on human population, it is still an understudied and unexplored research area. csom is a leading cause of hearing loss and life-threatening central nervous system complications. bacterial exposure especially pseudomo ...201626973629
genomic approaches for understanding dengue: insights from the virus, vector, and host.the incidence and geographic range of dengue have increased dramatically in recent decades. climate change, rapid urbanization and increased global travel have facilitated the spread of both efficient mosquito vectors and the four dengue virus serotypes between population centers. at the same time, significant advances in genomics approaches have provided insights into host-pathogen interactions, immunogenetics, and viral evolution in both humans and mosquitoes. here, we review these advances an ...201626931545
proteomic approaches to uncovering virus-host protein interactions during the progression of viral infection.the integration of proteomic methods to virology has facilitated a significant breadth of biological insight into mechanisms of virus replication, antiviral host responses and viral subversion of host defenses. throughout the course of infection, these cellular mechanisms rely heavily on the formation of temporally and spatially regulated virus-host protein-protein interactions. reviewed here are proteomic-based approaches that have been used to characterize this dynamic virus-host interplay. sp ...026817613
distal-less induces elemental color patterns in junonia butterfly wings.the border ocellus, or eyespot, is a conspicuous color pattern element in butterfly wings. for two decades, it has been hypothesized that transcription factors such as distal-less (dll) are responsible for eyespot pattern development in butterfly wings, based on their expression in the prospective eyespots. in particular, it has been suggested that dll is a determinant for eyespot size. however, functional evidence for this hypothesis has remained incomplete, due to technical difficulties.201626937287
small rna profiling in dengue virus 2-infected aedes mosquito cells reveals viral pirnas and novel host mirnas.in aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small rnas, including small interfering rnas (sirnas), piwi interacting rnas (pirnas), and micrornas (mirnas). viral sirnas are at the core of the antiviral rna interference machinery, one of the key pathways that limit virus replication in invertebrates. besides sirnas, aedes mosquitoes and cells derived from these insects produce arbovirus-d ...201626914027
presynaptic serotonin 2a receptors modulate thalamocortical plasticity and associative learning.higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (pfc). alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. prefrontal serotonin (5-ht)2a receptors play an essential role in cortical network activity, but the mechanism underlying their modulation of glutamatergic transmission and plasticity at thalamocortical synapses remains largely unexplored. here, we show that ...201626903620
design of a titering assay for lentiviral vectors utilizing direct extraction of dna from transduced cells in microtiter plates.using lentiviral vector products in clinical applications requires an accurate method for measuring transduction titer. for vectors lacking a marker gene, quantitative polymerase chain reaction is used to evaluate the number of vector dna copies in transduced target cells, from which a transduction titer is calculated. immune design previously described an integration-deficient lentiviral vector pseudotyped with a modified sindbis virus envelope for use in cancer immunotherapy (vp02, of the zvex ...201626942209
interferon-inducible protein scotin interferes with hcv replication through the autolysosomal degradation of ns5a.hepatitis c virus (hcv) utilizes autophagy to promote its propagation. here we show the autophagy-mediated suppression of hcv replication via the endoplasmic reticulum (er) protein scotin. scotin overexpression inhibits hcv replication and infectious virion production in cells infected with cell culture-derived hcv. hcv nonstructural 5a (ns5a) protein, which is a critical factor for hcv rna replication, interacts with the ifn-β-inducible protein scotin, which transports ns5a to autophagosomes fo ...201626868272
transstadial effects of bti on traits of aedes aegypti and infection with dengue virus.most mosquito control efforts are primarily focused on reducing the adult population size mediated by reductions in the larval population, which should lower risk of disease transmission. although the aim of larviciding is to reduce larval abundance and thus recruitment of adults, nonlethal effects on adults are possible, including transstadial effects on phenotypes of adults such as survival and pathogen infection and transmission. in addition, the mortality induced by control efforts may act i ...201626871951
the interferon-stimulated gene ifi27l2a restricts west nile virus infection and pathogenesis in a cell-type- and region-specific manner.the mammalian host responds to viral infections by inducing expression of hundreds of interferon-stimulated genes (isgs). while the functional significance of many isgs has yet to be determined, their cell type and temporal nature of expression suggest unique activities against specific pathogens. using a combination of ectopic expression and gene silencing approaches in cell culture, we previously identified ifi27l2a as a candidate antiviral isg within neuronal subsets of the central nervous sy ...201526699642
low-fidelity polymerases of alphaviruses recombine at higher rates to overproduce defective interfering particles.low-fidelity rna-dependent rna polymerases for many rna virus mutators have been shown to confer attenuated phenotypes, presumably due to increased mutation rates. additionally, for many rna viruses, replication to high titers results in the production of defective interfering particles (dis) that also attenuate infection. we hypothesized that fidelity, recombination, and di production are tightly linked. we show that a sindbis virus mutator replicating at a high multiplicity of infection manife ...201526676773
identification of a nucleotide in 5' untranslated region contributing to virus replication and virulence of coxsackievirus a16.coxsackievirus a16 (ca16) and enterovirus 71 (ev71) are two main causative pathogens of hand, foot and mouth disease (hfmd). unlike ev71, virulence determinants of ca16, particularly within 5' untranslated region (5'utr), have not been investigated until now. here, a series of nucleotides present in 5'utr of lethal but not in non-lethal ca16 strains were screened by aligning nucleotide sequences of lethal circulating changchun ca16 and the prototype g10 as well as non-lethal shzh05 strains. a re ...201626861413
activation of rnase l is dependent on oas3 expression during infection with diverse human viruses.the 2',5'-oligoadenylate (2-5a) synthetase (oas)-rnase l system is an ifn-induced antiviral pathway. rnase l activity depends on 2-5a, synthesized by oas. although all three enzymatically active oas proteins in humans--oas1, oas2, and oas3--synthesize 2-5a upon binding dsrna, it is unclear which are responsible for rnase l activation during viral infection. we used clustered regularly interspaced short palindromic repeats (crispr)-crispr-associated protein-9 nuclease (cas9) technology to enginee ...201626858407
big data offers novel insights for oncolytic virus immunotherapy.large-scale assays, such as microarrays, next-generation sequencing and various "omics" technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (ovit) in the cancer setting. tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and function ...201626861383
inhibition of chikungunya virus replication by 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea(mbzm-n-ibt).chikungunya virus (chikv) infection is one of the most challenging human arboviral infections with global significance and without any specific antiviral. in this investigation, 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (mbzm-n-ibt) was synthesised as a molecular hybrid of 2-methyl benzimidazole and isatin-β-thiosemicarbazone and its anti-chikv property was evaluated. the release of infectious virus particles was calculated by plaque assay, expression profil ...201626843462
aβ-induced synaptic alterations require the e3 ubiquitin ligase nedd4-1.alzheimer's disease (ad) is a neurodegenerative disease in which patients experience progressive cognitive decline. a wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (aβ). specifically, it has been shown that aβ decreases surface ampars, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. the precise molecula ...026843640
the sd1 subdomain of venezuelan equine encephalitis virus capsid protein plays a critical role in nucleocapsid and particle assembly.venezuelan equine encephalitis virus (veev) is an important human and animal pathogen, for which no safe and efficient vaccines or therapeutic means have been developed. viral particle assembly and budding processes represent potential targets for therapeutic intervention. however, our understanding of the mechanistic process of veev assembly, rna encapsidation, and the roles of different capsid-specific domains in these events remain to be described. the results of this new study demonstrate th ...201526656680
lncrna oip5-as1/cyrano sponges rna-binding protein hur.the function of the vast majority of mammalian long noncoding (lnc) rnas remains unknown. here, analysis of a highly abundant mammalian lncrna, oip5-as1, known as cyrano in zebrafish, revealed that oip5-as1 reduces cell proliferation. in human cervical carcinoma hela cells, the rna-binding protein hur, which enhances cell proliferation, associated with oip5-as1 and stabilized it. tagging oip5-as1 with ms2 hairpins to identify associated micrornas revealed that mir-424 interacted with oip5-as1 an ...201626819413
seropositivity for west nile virus antibodies in patients affected by myasthenia gravis.myasthenia gravis (mg) is an autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal muscles. specific auto-antibodies against acetylcholine receptor (achr) are present in the majority of mg patients, although the main cause behind its development still remains unclear. recently mg development following west nile virus (wnv) infection has been described in patients without any earlier evidence of mg. it is known that infectious agents trigger immune response ...201626858791
apoptosis, autophagy and unfolded protein response pathways in arbovirus replication and pathogenesis.arboviruses are pathogens that widely affect the health of people in different communities around the world. recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern. the arbovirus infection and replication processes are complex, and many factors are involved in their regulation. apoptosis, autophagy and the unfolded protein r ...201626781343
overexpression of trim14 promotes tongue squamous cell carcinoma aggressiveness by activating the nf-κb signaling pathway.tongue squamous cells carcinoma (tscc) is one of the most lethal malignancies of oral cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. herein, we showed that tripartite motif containing 14(trim14) is markedly up-regulated in tscc cell lines and clinical tissues. immunohistochemical (ihc) analysis of 116 clinical tscc specimens revealed that trim14 expression was significantly correlated with the tnm classification (t: p = 0.01; n: p < 0.001; m: p < 0. ...026799420
structural studies of chikungunya virus-like particles complexed with human antibodies: neutralization and cell-to-cell transmission.chikungunya virus is a positive-stranded rna alphavirus. structures of chikungunya virus-like particles in complex with strongly neutralizing antibody fab fragments (8b10 and 5f10) were determined using cryo-electron microscopy and x-ray crystallography. by fitting the crystallographically determined structures of these fab fragments into the cryo-electron density maps, we show that fab fragments of antibody 8b10 extend radially from the viral surface and block receptor binding on the e2 glycopr ...201526537684
trehalose, an mtor-independent inducer of autophagy, inhibits human cytomegalovirus infection in multiple cell types.human cytomegalovirus (hcmv) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. previous studies have shown that the induction of autophagy can inhibit the replication of several different types of dna and rna viruses. the goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of hcmv. most prior studies have used agents that induce autop ...201526559848
status of hepatitis c virus vaccination: recent update.hepatitis c virus (hcv) infection is still a major public health problem worldwide since its first identification in 1989. at the start, hcv infection was post-transfusion viral infection, particularly in developing countries. recently, due to iv drug abuse, hcv infection became number one health problem in well-developed countries as well. following acute hcv infection, the innate immune response is triggered in the form of activated coordinated interaction of nk cells, dendritic cells and inte ...026811632
autophagy genes enhance murine gammaherpesvirus 68 reactivation from latency by preventing virus-induced systemic inflammation.host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. murine gammaherpesvirus 68 (mhv68) infection is characterized by latency in macrophages, and reactivation is inhibited by interferon-γ (ifn-γ). using a lysozyme-m-cre (lysmcre) expression system, we show that deletion of autophagy-related (atg) genes fip200, beclin 1, atg14, atg16l1, atg7, atg3, and atg5, in the myeloid compartment, inhibited mhv68 reactivation in macrophages. atg5 deficiency ...026764599
a viral mrna motif at the 3'-untranslated region that confers translatability in a cell-specific manner. implications for virus evolution.sindbis virus (sinv) mrnas contain several motifs that participate in the regulation of their translation. we have discovered a motif at the 3' untranslated region (utr) of viral mrnas, constituted by three repeated sequences, which is involved in the translation of both sinv genomic and subgenomic mrnas in insect, but not in mammalian cells. these data illustrate for the first time that an element present at the 3'-utr confers translatability to mrnas from an animal virus in a cell-specific man ...201626755446
hippocampal dendritic spines are segregated depending on their actin polymerization.dendritic spines are mushroom-shaped protrusions of the postsynaptic membrane. spines receive the majority of glutamatergic synaptic inputs. their morphology, dynamics, and density have been related to synaptic plasticity and learning. the main determinant of spine shape is filamentous actin. using frap, we have reexamined the actin dynamics of individual spines from pyramidal hippocampal neurons, both in cultures and in hippocampal organotypic slices. our results indicate that, in cultures, the ...201626881098
cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances.oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized phase iii clinical trial hurdle. both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. there is increasing interest in their combination with cytotoxic agents, radiotherapy and i ...201627579292
activation of the dna damage response by rna viruses.rna viruses are a genetically diverse group of pathogens that are responsible for some of the most prevalent and lethal human diseases. numerous viruses introduce dna damage and genetic instability in host cells during their lifecycles and some species also manipulate components of the dna damage response (ddr), a complex and sophisticated series of cellular pathways that have evolved to detect and repair dna lesions. activation and manipulation of the ddr by dna viruses has been extensively stu ...201626751489
detection of persistent chikungunya virus rna but not infectious virus in experimental vertical transmission in aedes aegypti from malaysia.vertical transmission may contribute to the maintenance of arthropod-borne viruses, but its existence in chikungunya virus (chikv) is unclear. experimental vertical transmission of infectious clones of chikv in aedes aegypti mosquitoes from malaysia was investigated. eggs and adult progeny from the second gonotrophic cycles of infected parental mosquitoes were tested. using polymerase chain reaction (pcr), 56.3% of pooled eggs and 10% of adult progeny had detectable chikv rna, but no samples had ...201526598564
characterization of ryden (c19orf66) as an interferon-stimulated cellular inhibitor against dengue virus replication.dengue virus (denv) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. however, no vaccine or specific antiviral is available for dengue. as seen in other rna viruses, the innate immune system plays a key role in controlling denv infection and disease outcome. although the interferon (ifn) response, which is central to host protective immunity, has been reported to limit denv replication, the molecular details of how denv infection is modulated ...201626735137
rnai and antiviral defense in the honey bee.honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. therefore, investigating the factors associated with high annual losses of honey bee colonies in the us is an important and active area of research. pathogen incidence and abundance correlate with colony collapse disorder- (ccd-) affected colonies in the us and colony losses in the us and in some european countries. honey bees are readily infected by single-strande ...201526798663
the phosphatidylserine and phosphatidylethanolamine receptor cd300a binds dengue virus and enhances infection.dengue virus (denv) is the etiological agent of the major human arboviral disease. we previously demonstrated that the tim and tam families of phosphatidylserine (ptdser) receptors involved in the phagocytosis of apoptotic cells mediate denv entry into target cells. we show here that human cd300a, a recently identified phospholipid receptor, also binds directly denv particles and enhances viral entry. cd300a facilitates infection of the four denv serotypes, as well as of other mosquito-borne vir ...201526468529
aberrant regulation of synchronous network activity by the attention-deficit/hyperactivity disorder-associated human dopamine d4 receptor variant d4.7 in the prefrontal cortex.the hd4.7 variant has been linked to attention-deficit/hyperactivity disorder (adhd); however, the underlying mechanism is unknown. we found that activation of hd4.7 induced over-suppression of glutamatergic excitatory network bursts and under-suppression of gabaergic inhibitory network bursts in the prefrontal cortex (pfc) circuitry. methylphenidate, a psychostimulant drug used to treat adhd, normalized the effects of hd4.7 on synchronous network bursts in pfc pyramidal neurons. the findings of ...201526541360
direct pcr of indigenous and invasive mosquito species: a time- and cost-effective technique of mosquito barcoding.millions of people die each year as a result of pathogens transmitted by mosquitoes. however, the morphological identification of mosquito species can be difficult even for experts. the identification of morphologically indistinguishable species, such as members of the anopheles maculipennis complex (diptera: culicidae), and possible hybrids, such as culex pipiens pipiens/culex pipiens molestus (diptera: culicidae), presents a major problem. in addition, the detection and discrimination of newly ...201526663040
characterization of a novel human-specific sting agonist that elicits antiviral activity against emerging alphaviruses.pharmacologic stimulation of innate immune processes represents an attractive strategy to achieve multiple therapeutic outcomes including inhibition of virus replication, boosting antitumor immunity, and enhancing vaccine immunogenicity. in light of this we sought to identify small molecules capable of activating the type i interferon (ifn) response by way of the transcription factor ifn regulatory factor 3 (irf3). a high throughput in vitro screen yielded 4-(2-chloro-6-fluorobenzyl)-n-(furan-2- ...201526646986
bagaza virus inhibits japanese encephalitis & west nile virus replication in culex tritaeniorhynchus & cx. quinquefasciatus mosquitoes.studies have shown that certain flaviviruses influence susceptibility of mosquitoes by inhibiting/enhancing replication of important flaviviruses. hence, a study was designed to determine whether bagaza virus (bagv), a flavivirus isolated from culex tritaeniorhynchus mosquitoes in india, alters susceptibility of cx. tritaeniorhynchus and cx. quinquefasciatus mosquitoes to japanese encephalitis (jev) and west nile viruses (wnv).026905241
mtor is essential for corticosteroid effects on hippocampal ampa receptor function and fear memory.glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. we examined how corticosterone regulates ampa receptors (ampars), which are crucial for synaptic plasticity and memory formation. combining a live imaging fluorescent recovery after photobleaching approach with the use of the ph-sensitive gfp-ampar tagging revealed that corticosterone enhances the ampar mobile fraction and increases synaptic trapping of am ...201526572647
self-assembling protein nanoparticles in the design of vaccines.for over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. nevertheless, many diseases are not yet preventable by vaccination. this large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, mo ...201526862374
chikungunya nsp2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine.chikungunya virus is the pathogenic alphavirus that causes chikungunya fever in humans. in the last decade millions of cases have been reported around the world from africa to asia to the americas. the alphavirus nsp2 protein is multifunctional and is considered to be pivotal to viral replication, as the nsp2 protease activity is critical for proteolytic processing of the viral polyprotein during replication. classically the alphavirus nsp2 protease is thought to be papain-like with the enzyme r ...201526597768
conformational ensemble of the poliovirus 3cd precursor observed by md simulations and confirmed by saxs: a strategy to expand the viral proteome?the genomes of rna viruses are relatively small. to overcome the small-size limitation, rna viruses assign distinct functions to the processed viral proteins and their precursors. this is exemplified by poliovirus 3cd protein. 3c protein is a protease and rna-binding protein. 3d protein is an rna-dependent rna polymerase (rdrp). 3cd exhibits unique protease and rna-binding activities relative to 3c and is devoid of rdrp activity. the origin of these differences is unclear, since crystal structur ...201526610545
design, synthesis, and antiviral activity of novel ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates.a novel series of ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates was synthesized through the kabachnik-fields reaction using i2 as catalyst followed by copper-catalyzed cycloaddition of the azide-alkyne reaction (cuaac). all structures of the newly prepared compounds were characterized by (1) h nmr, (13) c nmr, and hrms spectra. the structures of 2e, 2f, 3d, and 3g were further confirmed by x-ray diffraction analysis. these compounds were tested against various strains of dna and rna ...201526575425
chikungunya virus replication in salivary glands of the mosquito aedes albopictus.chikungunya virus (chikv) is an emerging arbovirus transmitted to humans by mosquitoes such as aedes albopictus. to be transmitted, chikv must replicate in the mosquito midgut, then disseminate in the hemocele and infect the salivary glands before being released in saliva. we have developed a standardized protocol to visualize viral particles in the mosquito salivary glands using transmission electron microscopy. here we provide direct evidence for chikv replication and storage in ae. albopictus ...201526593936
microbiota-dependent priming of antiviral intestinal immunity in drosophila.enteric pathogens must overcome intestinal defenses to establish infection. in drosophila, the erk signaling pathway inhibits enteric virus infection. the intestinal microflora also impacts immunity but its role in enteric viral infection is unknown. here we show that two signals are required to activate antiviral erk signaling in the intestinal epithelium. one signal depends on recognition of peptidoglycan from the microbiota, particularly from the commensal acetobacter pomorum, which primes th ...026567510
both rig-i and mda5 detect alphavirus replication in concentration-dependent mode.alphaviruses are a family of positive-strand rna viruses that circulate on all continents between mosquito vectors and vertebrate hosts. despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus-host interaction are insufficiently understood. in this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. our new da ...201526550947
region-specific dendritic simplification induced by aβ, mediated by tau via dysregulation of microtubule dynamics: a mechanistic distinct event from other neurodegenerative processes.dendritic simplification, a key feature of the neurodegenerative triad of alzheimer's disease (ad) in addition to spine changes and neuron loss, occurs in a region-specific manner. however, it is unknown how changes in dendritic complexity are mediated and how they relate to spine changes and neuron loss.201526541821
beclin 1-vps34 complex architecture: understanding the nuts and bolts of therapeutic targets.autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. dysregulation of autophagy is linked to a growing number of human diseases. the beclin 1-vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. manipulation of autophagy, in particular via modulation of the action of the beclin 1-vps34 complexes, is considered a ...201526692106
an odyssey in antiviral drug development-50 years at the rega institute: 1964-2014. 201526713268
dendritic cell targeted vaccines: recent progresses and challenges.dendritic cells (dcs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (apcs), as well as the strongest functional antigen presenting cells, which can absorb, process and present antigens. as the key regulators of innate and adaptive immune responses, dcs are at the center of the immune system and capable of interacting with both b cells and t cells, thereby manipulating the humoral and cellular immune responses. dcs provide an es ...026513200
pros and cons of antigen-presenting cell targeted tumor vaccines.in therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. this review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted a ...201526583156
viral interference and persistence in mosquito-borne flaviviruses.mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. however, the epidemiological impact remains to be determined. mosquito-borne flaviviruses are primarily transmitted through aedes and culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. this establishment requires a balance between virus replication and the ...201526583158
hiv vaccine: recent advances, current roadblocks, and future directions.hiv/aids is a leading cause of mortality and morbidity worldwide. in spite of successful interventions and treatment protocols, an hiv vaccine would be the ultimate prevention and control strategy. ever since identification of hiv/aids, there have been meticulous efforts for vaccine development. the specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. recombinant dna technologies greatly facil ...201526579546
parp9-dtx3l ubiquitin ligase targets host histone h2bj and viral 3c protease to enhance interferon signaling and control viral infection.enhancing the response to interferon could offer an immunological advantage to the host. in support of this concept, we used a modified form of the transcription factor stat1 to achieve hyper-responsiveness to interferon without toxicity and markedly improve antiviral function in transgenic mice and transduced human cells. we found that the improvement depended on expression of a parp9-dtx3l complex with distinct domains for interaction with stat1 and for activity as an e3 ubiquitin ligase that ...201526479788
serological evidence of chikungunya virus among acute febrile patients in southern mozambique.in the last two decades, chikungunya virus (chikv) has rapidly expanded to several geographical areas, causing frequent outbreaks in sub-saharan africa, south east asia, south america, and europe. therefore, the disease remains heavily neglected in mozambique, and no recent study has been conducted.201526473605
mouse superkiller-2-like helicase ddx60 is dispensable for type i ifn induction and immunity to multiple viruses.ifn-α/β allow cells to fight virus infection by inducing the expression of many genes that encode effectors of antiviral defense. one of these, the ski2-like dexh-box helicase ddx60, was recently implicated in resistance of human cells to hepatitis c virus, as well as in induction of ifn-α/β by retinoic acid inducible gene 1-like receptors (rlrs) that detect the presence of rna viruses in a cell-intrinsic manner. here, we sought to investigate the role of ddx60 in ifn-α/β induction and in resist ...201526457795
simultaneous determination of sample thickness, tilt, and electron mean free path using tomographic tilt images based on beer-lambert law.cryo-electron tomography (cryo-et) is an emerging technique that can elucidate the architecture of macromolecular complexes and cellular ultrastructure in a near-native state. some important sample parameters, such as thickness and tilt, are needed for 3-d reconstruction. however, these parameters can currently only be determined using trial 3-d reconstructions. accurate electron mean free path plays a significant role in modeling image formation process essential for simulation of electron micr ...201526433027
hur and ago2 bind the internal ribosome entry site of enterovirus 71 and promote virus translation and replication.ev71 (enterovirus 71) rna contains an internal ribosomal entry site (ires) that directs cap-independent initiation of translation. ires-dependent translation requires the host's translation initiation factors and ires-associated trans-acting factors (itafs). we reported recently that mrna decay factor auf1 is a negative-acting itaf that binds ires stem-loop ii. we also reported that the small rna-processing enzyme dicer produces at least four small rnas (vsrnas) from the ev71 ires. one of these, ...201526451954
serum levels of inflammatory cytokines in rift valley fever patients are indicative of severe disease.rift valley fever (rvf) is a mosquito-borne viral zoonosis affecting domestic and wild ruminants, camels and humans. outbreaks of rvf are characterized by a sudden onset of abortions and high mortality amongst domestic ruminants. humans develop disease ranging from a mild flu-like illness to more severe complications including hemorrhagic syndrome, ocular and neurological lesions and death. during the rvf outbreak in south africa in 2010/11, a total of 278 human cases were laboratory confirmed, ...201526437779
2-(2,4-dioxy-1,2,3,4-tetrahydropyrimidin-1-yl)-n-(4-phenoxyphenyl)-acetamides as a novel class of cytomegalovirus replication inhibitors.a series of novel uracil derivatives, bearing n-(4-phenoxyphenyl)acetamide moiety at n3 of a pyrimidine ring, has been synthesized. their antiviral activity has been evaluated. it has been found that the novel compounds possess high inhibitory activity against replication of human cytomegalovirus (ad-169 and davis strains) in hel cell cultures. in addition, some of the derivatives proved to be inhibitory against varicella zoster virus.026798502
immune surveillance of the cns following infection and injury.the central nervous system (cns) contains a sophisticated neural network that must be constantly surveyed in order to detect and mitigate a diverse array of challenges. the innate and adaptive immune systems actively participate in this surveillance, which is critical for the maintenance of cns homeostasis and can facilitate the resolution of infections, degeneration, and tissue damage. infections and sterile injuries represent two common challenges imposed on the cns that require a prompt immun ...026431941
virus-based nanoparticles as versatile nanomachines.nanoscale engineering is revolutionizing the way we prevent, detect, and treat diseases. viruses have played a special role in these developments because they can function as prefabricated nanoscaffolds that have unique properties and are easily modified. the interiors of virus particles can encapsulate and protect sensitive compounds, while the exteriors can be altered to display large and small molecules in precisely defined arrays. these properties of viruses, along with their innate biocompa ...201526958921
intracellular mono-adp-ribosylation in signaling and disease.a key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. moreover detailed knowledge about these mechanisms and pathways helps to elucidate ...201526426055
infectious bronchitis coronavirus inhibits stat1 signaling and requires accessory proteins for resistance to type i interferon activity.the innate immune response is the first line of defense against viruses, and type i interferon (ifn) is a critical component of this response. similar to other viruses, the gammacoronavirus infectious bronchitis virus (ibv) has evolved under evolutionary pressure to evade and counteract the ifn response to enable its survival. previously, we reported that ibv induces a delayed activation of the ifn response. in the present work, we describe the resistance of ibv to ifn and the potential role of ...201526401035
antiviral potential of algae polysaccharides isolated from marine sources: a review.from food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate c ...201526484353
colorimetric detection of dengue by single tube reverse-transcription-loop-mediated isothermal amplification.dengue is usually diagnosed by isolation of the virus, serology or molecular diagnostic methods. several commercial kits for the diagnosis of dengue are existing, but concerns have arisen regarding to the affordability and performance characteristics of these kits. hence, the loop-mediated isothermal amplification (lamp) is potentially ideal to be used especially in resource limited environments. serum was collected from healthy donors and patients diagnosed with dengue infection. rna extracted ...201526384248
in vivo two-photon imaging of dendritic spines in marmoset neocortex(1,2,3).two-photon microscopy in combination with a technique involving the artificial expression of fluorescent protein has enabled the direct observation of dendritic spines in living brains. however, the application of this method to primate brains has been hindered by the lack of appropriate labeling techniques for visualizing dendritic spines. here, we developed an adeno-associated virus vector-based fluorescent protein expression system for visualizing dendritic spines in vivo in the marmoset neoc ...201526465000
retargeting oncolytic vesicular stomatitis virus to human t-cell lymphotropic virus type 1-associated adult t-cell leukemia.adult t cell leukemia/lymphoma (atl) is an aggressive cancer of cd4/cd25(+) t lymphocytes, the etiological agent of which is human t-cell lymphotropic virus type 1 (htlv-1). atl is highly refractory to current therapies, making the development of new treatments a high priority. oncolytic viruses such as vesicular stomatitis virus (vsv) are being considered as anticancer agents since they readily infect transformed cells compared to normal cells, the former appearing to exhibit defective innate i ...201526378177
regulation of cell death by iaps and their antagonists.inhibitors of apoptosis (iaps) family of genes encode baculovirus iap-repeat domain-containing proteins with antiapoptotic function. these proteins also contain ring or ubc domains and act by binding to major proapoptotic factors and ubiquitylating them. high levels of iaps inhibit caspase-mediated apoptosis. for these cells to undergo apoptosis, iap function must be neutralized by iap-antagonists. mammalian iap knockouts do not exhibit obvious developmental phenotypes, but the cells are more se ...201526431568
fiat luc: bioluminescence imaging reveals in vivo viral replication dynamics. 201526356297
kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 1 interacts with a member of the interferon-stimulated gene 15 pathway.kaposi's sarcoma-associated herpesvirus (kshv) is a gammaherpesvirus known to establish lifelong latency in the human host. we and others have previously shown that three kshv homologs of cellular interferon regulatory factors (irfs), known as viral irfs (virfs), participate in evasion of the host interferon (ifn) response. we report that virf1 interacts with the cellular interferon-stimulated gene 15 (isg15) e3 ligase, herc5, in the context of toll-like receptor 3 (tlr3) activation and ifn indu ...201526355087
hur displaces polypyrimidine tract binding protein to facilitate la binding to the 3' untranslated region and enhances hepatitis c virus replication.hur is a ubiquitous, rna binding protein that influences the stability and translation of several cellular mrnas. here, we report a novel role for hur, as a regulator of proteins assembling at the 3' untranslated region (utr) of viral rna in the context of hepatitis c virus (hcv) infection. hur relocalizes from the nucleus to the cytoplasm upon hcv infection, interacts with the viral polymerase (ns5b), and gets redistributed into compartments of viral rna synthesis. depletion in hur levels leads ...201526339049
structural and functional characterization of anti-a33 antibodies reveal a potent cross-species orthopoxviruses neutralizer.vaccinia virus a33 is an extracellular enveloped virus (eev)-specific type ii membrane glycoprotein that is essential for efficient eev formation and long-range viral spread within the host. a33 is a target for neutralizing antibody responses against eev. in this study, we produced seven murine anti-a33 monoclonal antibodies (mabs) by immunizing mice with live vacv, followed by boosting with the soluble a33 homodimeric ectodomain. five a33 specific mabs were capable of neutralizing eev in the pr ...201526325270
selective effects of pde10a inhibitors on striatopallidal neurons require phosphatase inhibition by darpp-32(1,2,3).type 10a phosphodiesterase (pde10a) is highly expressed in the striatum, in striatonigral and striatopallidal medium-sized spiny neurons (msns), which express d1 and d2 dopamine receptors, respectively. pde10a inhibitors have pharmacological and behavioral effects suggesting an antipsychotic profile, but the cellular bases of these effects are unclear. we analyzed the effects of pde10a inhibition in vivo by immunohistochemistry, and imaged camp, camp-dependent protein kinase a (pka), and cgmp si ...201526465004
flavivirus sfrna suppresses antiviral rna interference in cultured cells and mosquitoes and directly interacts with the rnai machinery.productive arbovirus infections require mechanisms to suppress or circumvent the cellular rna interference (rnai) pathway, a major antiviral response in mosquitoes. in this study, we demonstrate that two flaviviruses, dengue virus and kunjin virus, significantly repress sirna-mediated rnai in infected human cells as well as during infection of the mosquito vector culex quinquefasciatus. arthropod-borne flaviviruses generate a small structured non-coding rna from the viral 3' utr referred to as s ...201526331679
cd8 t-cell priming upon mrna vaccination is restricted to bone-marrow-derived antigen-presenting cells and may involve antigen transfer from myocytes.self-amplifying mrnas (sam(®) ) are a novel class of nucleic acid vaccines, delivered by a non-viral delivery system. they are effective at eliciting potent and protective immune responses and are being developed as a platform technology with potential to be used for a broad range of targets. however, their mechanism of action has not been fully elucidated. to date, no evidence of in vivo transduction of professional antigen-presenting cells (apcs) by sam vector has been reported, while the anti ...201526173587
rate of novel host invasion affects adaptability of evolving rna virus lineages.although differing rates of environmental turnover should be consequential for the dynamics of adaptive change, this idea has been rarely examined outside of theory. in particular, the importance of rna viruses in disease emergence warrants experiments testing how differing rates of novel host invasion may impact the ability of viruses to adaptively shift onto a novel host. to test whether the rate of environmental turnover influences adaptation, we experimentally evolved 144 sindbis virus linea ...026246544
x-ray structural and functional studies of the three tandemly linked domains of non-structural protein 3 (nsp3) from murine hepatitis virus reveal conserved functions.murine hepatitis virus (mhv) has long served as a model system for the study of coronaviruses. non-structural protein 3 (nsp3) is the largest nsp in the coronavirus genome, and it contains multiple functional domains that are required for coronavirus replication. despite the numerous functional studies on mhv and its nsp3 domain, the structure of only one domain in nsp3, the small ubiquitin-like domain 1 (ubl1), has been determined. we report here the x-ray structure of three tandemly linked dom ...201526296883
comparative mapping of host-pathogen protein-protein interactions.pathogens usurp a variety of host pathways via protein-protein interactions to ensure efficient pathogen replication. despite the existence of an impressive toolkit of systematic and unbiased approaches, we still lack a comprehensive list of these ppis and an understanding of their functional implications. here, we highlight the importance of harnessing genetic diversity of hosts and pathogens for uncovering the biochemical basis of pathogen restriction, virulence, fitness, and pathogenesis. we ...201526275922
hexokinase 2 controls cellular stress response through localization of an rna-binding protein.subcellular localization of rna-binding proteins is a key determinant of their ability to control rna metabolism and cellular stress response. using an rnai-based kinome-wide screen, we identified hexokinase 2 (hk2) as a regulator of the cytoplasmic accumulation of hnrnp a1 in response to hypertonic stress and human rhinovirus infection (hrv). we show that inhibition of hk2 expression or pharmacological inhibition of hk2 activity blocks the cytoplasmic accumulation of heterogeneous nuclear ribon ...201526247723
oncolytic potency of her-2 retargeted vsv-fh hybrid viruses: the role of receptor ligand affinity.the hybrid oncolytic vesicular stomatitis virus (vsv-fh) deleted for its g glycoprotein and displaying the measles virus (mv) envelope glycoproteins (hemagglutinin h and fusion f) is fusogenic, infects cells via any of the three mv receptors and has potent oncolytic activity against subcutaneous and disseminated myeloma tumors. to tailor vsv-fh as an oncolytic virus for ovarian cancer, we ablated its natural tropism and retargeted the virus by display of a single-chain antibody (scfv) with speci ...201527119107
potential antileukemia effect and structural analyses of srpk inhibition by n-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (srpin340).dysregulation of pre-mrna splicing machinery activity has been related to the biogenesis of several diseases. the serine/arginine-rich protein kinase family (srpks) plays a critical role in regulating pre-mrna splicing events through the extensive phosphorylation of splicing factors from the family of serine/arginine-rich proteins (sr proteins). previous investigations have described the overexpression of srpk1 and srpk2 in leukemia and other cancer types, suggesting that they would be useful ta ...201526244849
analysis of site-specific n-glycan remodeling in the endoplasmic reticulum and the golgi.the hallmark of n-linked protein glycosylation is the generation of diverse glycan structures in the secretory pathway. dynamic, non-template-driven processes of n-glycan remodeling in the endoplasmic reticulum and the golgi provide the cellular setting for structural diversity. we applied newly developed mass spectrometry-based analytics to quantify site-specific n-glycan remodeling of the model protein pdi1p expressed in insect cells. molecular dynamics simulation, mutational analysis, kinetic ...201526240167
mammalian synthetic circuits with rna binding proteins for rna-only delivery.synthetic regulatory circuits encoded in rna rather than dna could provide a means to control cell behavior while avoiding potentially harmful genomic integration in therapeutic applications. we create post-transcriptional circuits using rna-binding proteins, which can be wired in a plug-and-play fashion to create networks of higher complexity. we show that the circuits function in mammalian cells when encoded in modified mrna or self-replicating rna.201526237515
antiviral defense mechanisms in honey bees.honey bees are significant pollinators of agricultural crops and other important plant species. high annual losses of honey bee colonies in north america and in some parts of europe have profound ecological and economic implications. colony losses have been attributed to multiple factors including rna viruses, thus understanding bee antiviral defense mechanisms may result in the development of strategies that mitigate colony losses. honey bee antiviral defense mechanisms include rna-interference ...026273564
the new vaccines: building viruses that elicit antitumor immunity.whereas cancer cells are poor immunogens, some viruses are capable of eliciting powerful and lifelong immunity. recombinant viruses and plasmid dna encoding tumor-associated antigens can elicit powerful and specific immune responses that can be enhanced by the use of cytokines and costimulatory molecules. these immune responses have destroyed growing tumor cells in experimental animal models. for the first time, immunotherapeutic strategies that employ recombinant viruses are being tested in cli ...08902391
unraveling host-vector-arbovirus interactions by two-gene high resolution melting mosquito bloodmeal analysis in a kenyan wildlife-livestock interface.the blood-feeding patterns of mosquitoes are directly linked to the spread of pathogens that they transmit. efficient identification of arthropod vector bloodmeal hosts can identify the diversity of vertebrate species potentially involved in disease transmission cycles. while molecular bloodmeal analyses rely on sequencing of cytochrome b (cyt b) or cytochrome oxidase 1 gene pcr products, recently developed bloodmeal host identification based on high resolution melting (hrm) analyses of cyt b pc ...201526230507
effect of osmotic pressure on the stability of whole inactivated influenza vaccine for coating on microneedles.enveloped virus vaccines can be damaged by high osmotic strength solutions, such as those used to protect the vaccine antigen during drying, which contain high concentrations of sugars. we therefore studied shrinkage and activity loss of whole inactivated influenza virus in hyperosmotic solutions and used those findings to improve vaccine coating of microneedle patches for influenza vaccination. using stopped-flow light scattering analysis, we found that the virus underwent an initial shrinkage ...201526230936
antiviral phosphorodiamidate morpholino oligomers are protective against chikungunya virus infection on cell-based and murine models.chikungunya virus (chikv) infection in human is associated with debilitating and persistent arthralgia and arthritis. currently, there is no specific vaccine or effective antiviral available. anti-chikv phosphorodiamidate morpholino oligomer (cpmo) was evaluated for its antiviral efficacy and cytotoxcity in human cells and neonate murine model. two cpmos were designed to block translation initiation of a highly conserved sequence in chikv non-structural and structural polyprotein, respectively. ...201526224141
herpes simplex virus 1 suppresses the function of lung dendritic cells via caveolin-1.caveolin-1 (cav-1), the principal structural protein of caveolae, has been implicated as a regulator of virus-host interactions. several viruses exploit caveolae to facilitate viral infections. however, the roles of cav-1 in herpes simplex virus 1 (hsv-1) infection have not fully been elucidated. here, we report that cav-1 downregulates the expression of inducible nitric oxide synthase (inos) and the production of nitric oxide (no) in dendritic cells (dcs) during hsv-1 infection. as a result, ca ...201526018534
quantitative proteomics identifies serum response factor binding protein 1 as a host factor for hepatitis c virus entry.hepatitis c virus (hcv) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor cd81. how cd81 governs hcv entry is poorly characterized, and cd81 protein interactions after virus binding remain elusive. we have developed a quantitative proteomics protocol to identify hcv-triggered cd81 interactions and found 26 dynamic binding partners. at least six of these proteins promote hcv infection, as indicated by rnai. we further characterized ser ...201526212323
designing herpes viruses as oncolytics.oncolytic herpes simplex virus (ohsv) was one of the first genetically-engineered oncolytic viruses. because herpes simplex virus (hsv) is a natural human pathogen that can cause serious disease, it is incumbent that it be genetically-engineered or significantly attenuated for safety. here we present a detailed explanation of the functions of hsv-1 genes frequently mutated to endow oncolytic activity. these genes are non-essential for growth in tissue culture cells but are important for growth i ...201526462293
going viral with fluorescent proteins.many longstanding questions about dynamics of virus-cell interactions can be answered by combining fluorescence imaging techniques with fluorescent protein (fp) tagging strategies. successfully creating a fp fusion with a cellular or viral protein of interest first requires selecting the appropriate fp. however, while viral architecture and cellular localization often dictate the suitability of a fp, a fp's chemical and physical properties must also be considered. here, we discuss the challenges ...201526202231
the interferon-inducible mouse apolipoprotein l9 and prohibitins cooperate to restrict theiler's virus replication.apolipoprotein l9b (apol9b) is an interferon-stimulated gene (isg) that has antiviral activity and is weakly expressed in primary mouse neurons as compared to other cell types. here, we show that both apol9 isoforms (apol9b and apol9a) inhibit replication of theiler's murine encephalomyelitis virus (tmev) but not replication of vesicular stomatitis virus (vsv), murid herpesvirus-4 (muhv-4), or infection by a lentiviral vector. apol9 genes are strongly expressed in mouse liver and, to a lesser ex ...201526196674
knockout silkworms reveal a dispensable role for juvenile hormones in holometabolous life cycle.insect juvenile hormones (jhs) prevent precocious metamorphosis and allow larvae to undergo multiple rounds of status quo molts. however, the roles of jhs during the embryonic and very early larval stages have not been fully understood. we generated and characterized knockout silkworms (bombyx mori) with null mutations in jh biosynthesis or jh receptor genes using genome-editing tools. we found that embryonic growth and morphogenesis are largely independent of jhs in bombyx and that, even in the ...201526195792
using the hepatitis c virus rna-dependent rna polymerase as a model to understand viral polymerase structure, function and dynamics.viral polymerases replicate and transcribe the genomes of several viruses of global health concern such as hepatitis c virus (hcv), human immunodeficiency virus (hiv) and ebola virus. for this reason they are key targets for therapies to treat viral infections. although there is little sequence similarity across the different types of viral polymerases, all of them present a right-hand shape and certain structural motifs that are highly conserved. these features allow their functional properties ...201526193306
autophagy knocked down by high-risk hpv infection and uterine cervical carcinogenesis.cervical cancer is a leading cause of cancer death among women in the world. the specific etiopathogenesis of cervical cancer is indeed complex. even so, we should make arduous efforts to have a precise understanding of the complicate cellular/molecular mechanisms underlying initiation, progression and/or prevention of the cervical cancer. the high-risk human papillomavirus (hrhpv) is considered as the major causative agent of cervical cancer. but with the existence of hrhpv only is not sufficie ...201526379821
ultraviolet light (uv) inactivation of porcine parvovirus in liquid plasma and effect of uv irradiated spray dried porcine plasma on performance of weaned pigs.a novel ultraviolet light irradiation (uv-c, 254 nm) process was designed as an additional safety feature for manufacturing of spray dried porcine plasma (sdpp). in exp. 1, three 10-l batches of bovine plasma were inoculated with 10(5.2 ± 0.12) tissue culture infectious dose 50 (tcid50) of porcine parvovirus (ppv) per ml of plasma and subjected to uv-c ranging from 0 to 9180 j/l. no viable ppv was detected in bovine plasma by micro-titer assay in sk6 cell culture after uv-c at 2295 j/l. in exp. ...201526171968
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