Journal Sciences News
Urban Forestry & Urban Greening
March 2018
Molecular dissection of distinct symptoms induced by tomato chlorosis virus and tomato yellow leaf curl virus based on comparative transcriptome analysis
Publication date: March 2018
Source:Virology, Volume 516 Author(s): Jang-Kyun Seo, Mi-Kyeong Kim, Hae-Ryun Kwak, Hong-Soo Choi, Moon Nam, Junkyoung Choe, Boram Choi, Soo-Jung Han, Jin-Ho Kang, Choonkyun Jung The viral infection of plants may cause various physiological symptoms associated with the reprogramming of plant gene expression. However, the molecular mechanisms and associated genes underlying disease symptom development in plants infected with viruses are largely unknown. In this study, we employed RNA sequencing for in-depth molecular characterization of the transcriptional changes associated with the development of distinct symptoms induced by tomato chlorosis virus (ToCV) and tomato yellow leaf curl virus (TYLCV) in tomato. Comparative analysis of differentially expressed genes revealed that ToCV and TYLCV induced distinct transcriptional changes in tomato and resulted in the identification of important genes responsible for the development of symptoms of ToCV (i.e., chlorosis and anthocyanin accumulation) and TYLCV (i.e., yellowing, stunted growth, and leaf curl). Our comprehensive transcriptome analysis can provide molecular strategies to reduce the severity of disease symptoms as well as new insights for the development of virus-resistant crops.
March 2018
Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins
Publication date: March 2018
Source:Virology, Volume 516 Author(s): Mingce Zhang, Tanya O. Robinson, Alexandra Duverger, Olaf Kutsch, Sonya L. Heath, Randy Q. Cron During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently represent the largest subpopulation of CD4 T cell subsets, implying relative resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture system. This suppression was mediated in part via multiple inhibitory surface proteins expressed on Tregs. Antibody blockade of CTLA-4, PD-1, and GARP on Tregs resulted in increased HIV-1 DNA integration and mRNA expression in neighboring CD4 T cells. Moreover, antibody blockade of Tregs inhibitory proteins resulted in increased HIV-1 LTR transcription in co-cultured CD4 T cells. Thus, Tregs inhibit HIV-1 infection of other CD4 T cell subsets via interactions with inhibitory cell surface proteins.

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March 2018
Progress toward an enhanced vaccine: Eight marked attenuated viruses to porcine reproductive and respiratory disease virus
Publication date: March 2018
Source:Virology, Volume 516 Author(s): Allyn Spear, Feng-Xue Wang, Matthew A. Kappes, Phani B. Das, Kay S. Faaberg Recombinant viruses of strain Ingelvac PRRS porcine reproductive and respiratory syndrome virus (PRRSV) modified live virus vaccine were produced with two individual small in-frame deletions in nonstructural protein 2 (nsp2;
March 2018
Evaluation of the zoonotic potential of multiple subgroups of clade 2.3.4.4 influenza A (H5N8) virus
Publication date: March 2018
Source:Virology, Volume 516 Author(s): Yu-Na Lee, Eun-Kyoung Lee, Byung-Min Song, Gyeong-Beom Heo, Sang-Hee Woo, Sun-Ha Cheon, Youn-Jeong Lee Clade 2.3.4.4 H5N8 highly pathogenic avian influenza viruses (HPAIVs) have spread worldwide. Phylogenetic analysis identified two genetic groups of the H5N8 HPAIVs in South Korea; group A evolved further into four subgroups. Here, we examined the zoonotic potential, both in vivo and in vitro, of genetically distinct subgroups of H5N8 HPAIVs isolated in South Korea. When compared with other subgroups, A/mallard/Korea/H2102/2015 (H2102) virus caused relatively severe disease in mice at high doses. In ferrets, all H5N8 viruses replicated restrictively in the respiratory tract and did not induce significant clinical signs of influenza infection. In vitro studies, all viruses displayed a hemagglutinin phenotype that was poorly adapted for infection of mammals, although the H2102 virus exhibited higher replication kinetics at 33C than the others. Although H5N8 HPAIVs have not yet acquired all the characteristics required for adaptation to mammals, their ability to evolve continuously underscores the need for timely risk assessment.
March 2018
Schmallenberg virus non-structural protein NSm: Intracellular distribution and role of non-hydrophobic domains
Publication date: March 2018
Source:Virology, Volume 516 Author(s): Franziska Kraatz, Kerstin Wernike, Sven Reiche, Andrea Aebischer, Ilona Reimann, Martin Beer Schmallenberg virus (SBV) induces fetal malformation, abortions and stillbirth in ruminants. While the non-structural protein NSs is a major virulence factor, the biological function of NSm, the second non-structural protein which consists of three hydrophobic transmembrane (I, III, V) and two non-hydrophobic regions (II, IV), is still unknown. Here, a series of NSm mutants displaying deletions of nearly the entire NSm or of the non-hydrophobic domains was generated and the intracellular distribution of NSm was assessed. SBV-NSm is dispensable for the generation of infectious virus and mutants lacking domains II V showed growth properties similar to the wild-type virus. In addition, a comparable intracellular distribution of SBV-NSm was observed in mammalian cells infected with domain II mutants or wild-type virus. In both cases, NSm co-localized with the glycoprotein Gc in the Golgi compartment. However, domain IV-deletion mutants showed an altered distribution pattern and no co-localization of NSm and Gc.
February 2018
The interactome of EBV LMP1 evaluated by proximity-based BioID approach
Publication date: March 2018
Source:Virology, Volume 516 Author(s): Mark A. Rider, Mujeeb R. Cheerathodi, Stephanie N. Hurwitz, Dingani Nkosi, Lauren A. Howell, Deanna C. Tremblay, Xia Liu, Fanxiu Zhu, David G. Meckes Epstein-Barr virus LMP1 is an oncoprotein required for immortalizing B lymphocytes and also plays important roles in transforming non-lymphoid tissue. The discovery of LMP1 protein interactions will likely generate targets to treat EBV-associated cancers. Here, we define the broader LMP1 interactome using the recently developed BioID method. Combined with mass spectrometry, we identified over 1000 proteins across seven independent experiments with direct or indirect relationships to LMP1. Pathway analysis suggests that a significant number of the proteins identified are involved in signal transduction and protein or vesicle trafficking. Interestingly, a large number of proteins thought to be important in the formation of exosomes and protein targeting were recognized as probable LMP1 interacting partners, including CD63, syntenin-1, ALIX, TSG101, HRS, CHMPs, and sorting nexins. Therefore, it is likely that LMP1 modifies protein trafficking and exosome biogenesis pathways. In support of this, knock-down of syntenin-1 and ALIX resulted in reduced exosomal LMP1.
February 2018
In vitro models for deciphering the mechanisms underlying the sexual transmission of viruses at the mucosal level
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Julie Frouard, Anna Le Tortorec, Nathalie Dejucq-Rainsford Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of entry into the organism of viruses transmitted through sexual intercourse is a necessary prerequisite to the design of treatments to block those infections, in vitro modeling of the transmission is essential. The aim of this review is to present the models and methodologies available for the in vitro study of the interactions between viruses and mucosal tissue and for the preclinical evaluation of antiviral compounds, and to point out their advantages and limitations according to the question being studied.
February 2018
The eukaryotic translation initiation factor 3 subunit E binds to classical swine fever virus NS5A and facilitates viral replication
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Xiaofeng Liu, Xiaoyu Wang, Qian Wang, Mingyang Luo, Huancheng Guo, Wenjie Gong, Changchun Tu, Jinfu Sun Classical swine fever virus (CSFV) NS5A protein is a multifunctional protein, playing critical roles in viral RNA replication, translation and assembly. To further explore its functions in viral replication, interaction of NS5A with host factors was assayed using a his-tag pull down assay coupled with shotgun LC-MS/MS. Host protein translation initiation factor 3 subunit E was identified as a binding partner of NS5A, and confirmed by co-immunoprecipitation and co-localization analysis. Overexpression of eIF3E markedly enhanced CSFV genomic replication, viral protein expression and production of progeny virus, and downregulation of eIF3E by siRNA significantly decreased viral proliferation in PK-15 cells. Luciferase reporter assay showed an enhancement of translational activity of the internal ribosome entry site of CSFV by eIF3E and a decrease in cellular translation by NS5A. These data indicate that eIF3E plays an important role in CSFV replication, thereby identifying it as a potential target for inhibition of the virus.

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February 2018
A novel peptide-based vaccine candidate with protective efficacy against influenza A in a mouse model
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Jos
February 2018
A multiplex real-time RT-PCR for simultaneous detection of four most common avian respiratory viruses
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Nacira Laamiri, Rim Aouini, Boutheina Marnissi, Abdeljelil Ghram, Issam Hmila A one-step multiplex real-time reverse transcription-PCR (rRT-PCR) assay was developed for simultaneous detection and quantification of four avian respiratory viruses: avian influenza virus (AIV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV) and infectious laryngotracheitis virus (ILTV). In comparison with the singleplex rRT-PCR, the specificity, the sensitivity and the reproducibility of the new assay were evaluated and validated using 70 clinical samples. The optimal cutoff point, the corresponding limit of quantification (LoQ) and the limit of detection (LoD) were statistical established based on receiver operating characteristic (ROC) curve analysis. The results showed that the multiplex assay presents higher sensitivity and specificity. Correlation coefficients (R2) and amplification efficiencies (E) of all singleplex and multiplex rRT-PCR reactions are within the acceptable range. The 95% LoDs of multiplex assay were in the range [319] copies genomic/ l, and its corresponding cutoff cycles were in the range [34.1636.59]. No competitive inhibition for the detection of the four targets and no specific amplification or cross reactivity with other tested viruses was observed. Excellent results were attained in the inter-assay and intra-assay reproducibility evaluation. All identified samples by the multiplex rRT-PCR assay proved to be 100% concordant with the results of the singleplex assays. The results achieved showed that the multiplex assay is very suitable as a routine laboratory test for rapid and specific detection and quantification of co-infections in field samples.
February 2018
Envelope glycoproteins sampling states 2/3 are susceptible to ADCC by sera from HIV-1-infected individuals
Publication date: February 2018
Source:Virology, Volume 515 Author(s): J
February 2018
Localization to detergent-resistant membranes and HIV-1 core entry inhibition correlate with HIV-1 restriction by SERINC5
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Bianca Schulte, Anastasia Selyutina, Silvana Opp, Alon Herschhorn, Joseph G. Sodroski, Massimo Pizzato, Felipe Diaz-Griffero SERINC5(S5) is a multi-span transmembrane protein that potently blocks the infectivity of HIV-1 produced by human T-cells. The ability of S5 to restrict infectivity correlates with its presence in the virion, but the exact mechanism by which S5 restricts HIV-1 is unknown. Here we tested whether the core from HIV-1 virions containing S5 is delivered to the cytoplasm. Using the fate of the capsid assay, we demonstrated that the viral core of S5-restricted HIV-1 does not reach the cytoplasm of target cells, suggesting a block in the delivery of the core to the cytoplasm. In agreement with evidence suggesting that the viral determinants for S5 restriction map to the envelope of HIV-1, we observed that S5 induces conformational changes to the HIV-1 envelope. Further, we demonstrated that S5 localizes to detergent-resistant membranes (DRMs), as has been shown previously for the HIV-1 envelope in producer cells. In order to identify the determinants of S5 restriction, we explored the ability of all human SERINC proteins to restrict HIV-1. In contrast to human S5, we observed that human SERINC2(S2) did not restrict HIV-1, and was inefficiently incorporated into HIV-1 virions when compared to S5. Experiments using S5-S2 chimeric proteins revealed two functional domains for restriction: one necessary for S5 incorporation into virions, which does not seem to be necessary for restriction, and a second one necessary to change the HIV-1 envelope conformation, localize to DRMs, and block infection.
February 2018
The level of midgut penetration of two begomoviruses affects their acquisition and transmission by two species of Bemisia tabaci
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Tao Guo, Jing Zhao, Li-Long Pan, Liang Geng, Teng Lei, Xiao-Wei Wang, Shu-Sheng Liu Begomoviruses are transmitted by whiteflies in a persistent manner, but factors responsible for the variation of virus transmission by different species are poorly understood. We examined ingestion of papaya leaf curl China virus (PaLCuCNV) and tomato yellow leaf curl virus (TYLCV) by two species of the Bemisia tabaci complex, MEAM1 and MED, and then quantified the virion concentrations in different organs/tissues in each species. We found that PaLCuCNV penetrated the midgut wall of MED less efficiently than MEAM1, resulting in lower efficiency of PalCuCNV transmission by MED than that by MEAM1, while TYLCV penetrated the midgut wall of both species and was transmitted by them at similar levels of efficiency. Virus coat protein determined the virus capacity to cross the midgut wall of a given whitefly species. These data indicate that the level of midgut penetration determines virus acquisition and transmission by whiteflies in the first instance.
February 2018
Strand-like structures and the nonstructural proteins 5, 3 and 1 are present in the nucleus of mosquito cells infected with dengue virus
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Jos
February 2018
The unique two-component tail sheath of giant Pseudomonas phage PaBG
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Lidia P. Kurochkina, Pavel I. Semenyuk, Nina N. Sykilinda, Konstantin A. Miroshnikov Myoviridae bacteriophages have a special contractile tail machine that facilitates high viral infection efficiency. The major component of this machine is a tail sheath that contracts during infection, allowing delivery of viral DNA into the host cell. Tail sheaths of Myoviridae phages are composed of multiple copies of individual proteins. The giant Pseudomonas aeruginosa phage PaBG is notable in its possession of two tail sheath proteins. These tail sheath proteins are encoded by orf 76 and 204, which were cloned and expressed individually and together in Escherichia coli. We demonstrate that only co-expression of both genes results in efficient assembly of thermostable and proteolytically resistant polysheaths composed of gp76 and gp204 with approximately 1:1 stoichiometry. Both gp76 and gp204 have been identified as structural components of the virion particle. We conclude that during PaBG morphogenesis in vivo two proteins, gp76 and gp204, assemble the tail sheath.
February 2018
Studies on immunity and immunopathogenesis of parrot bornaviral disease in cockatiels
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Samer Sadeq Hameed, Jianhua Guo, Ian Tizard, H.L. Shivaprasad, Susan Payne We have demonstrated that vaccination of cockatiels (Nymphicus hollandicus) with killed parrot bornavirus (PaBV) plus recombinant PaBV-4 nucleoprotein (N) in alum was protective against disease in birds challenged with a virulent bornavirus isolate (PaBV-2). Unvaccinated birds, as well as birds vaccinated after challenge, developed gross and histologic lesions typical of proventricular dilatation disease (PDD). There was no evidence that vaccination either before or after challenge made the infection more severe. Birds vaccinated prior to challenge largely remained free of disease, despite the persistence of the virus in many organs. Similar results were obtained when recombinant N, in alum, was used for vaccination. In some rodent models, Borna disease is immune mediated thus we did an additional study whereby cyclosporine A was administered to unvaccinated birds starting 1day prior to challenge. This treatment also conferred complete protection from disease, but not infection.
February 2018
HIV internalization into oral and genital epithelial cells by endocytosis and macropinocytosis leads to viral sequestration in the vesicles
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Aizezi Yasen, Rossana Herrera, Kristina Rosbe, Kathy Lien, Sharof M. Tugizov Recently, we showed that HIV-1 is sequestered, i.e., trapped, in the intracellular vesicles of oral and genital epithelial cells. Here, we investigated the mechanisms of HIV-1 sequestration in vesicles of polarized tonsil, foreskin and cervical epithelial cells. HIV-1 internalization into epithelial cells is initiated by multiple entry pathways, including clathrin-, caveolin/lipid raft-associated endocytosis and macropinocytosis. Inhibition of HIV-1 attachment to galactosylceramide and heparan sulfate proteoglycans, and virus endocytosis and macropinocytosis reduced HIV-1 sequestration by 3040%. T-cell immunoglobulin and mucin domain 1 (TIM-1) were expressed on the apical surface of polarized tonsil, cervical and foreskin epithelial cells. However, TIM-1-associated HIV-1 macropinocytosis and sequestration were detected mostly in tonsil epithelial cells. Sequestered HIV-1 was resistant to trypsin, pronase, and soluble CD4, indicating that the sequestered virus was intracellular. Inhibition of HIV-1 intraepithelial sequestration and elimination of vesicles containing virus in the mucosal epithelium may help in the prevention of HIV-1 mucosal transmission.
February 2018
Landmarks of endosomal remodeling in the early phase of cytomegalovirus infection
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Ljerka Karleu
February 2018
Murine norovirus inhibits B cell development in the bone marrow of STAT1-deficient mice
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Charlie C. Hsu, Stacey M. Meeker, Sabine Escobar, Thea L. Brabb, Jisun Paik, Heon Park, Brian M. Iritani, Lillian Maggio-Price Noroviruses are a leading cause of gastroenteritis in humans and it was recently revealed that noroviruses can infect B cells. We demonstrate that murine norovirus (MNV) infection can significantly impair B cell development in the bone marrow in a signal transducer and activator of transcription 1 (STAT1) dependent, but interferon signaling independent manner. We also show that MNV replication is more pronounced in the absence of STAT1 in ex vivo cultured B cells. Interestingly, using bone marrow transplantation studies, we found that impaired B cell development requires Stat1 -/- hematopoietic cells and Stat1 -/- stromal cells, and that the presence of wild-type hematopoietic or stromal cells was sufficient to restore normal development of Stat1 -/- B cells. These results suggest that B cells normally restrain norovirus replication in a cell autonomous manner, and that wild-type STAT1 is required to protect B cell development during infection.
February 2018
The OC43 human coronavirus envelope protein is critical for infectious virus production and propagation in neuronal cells and is a determinant of neurovirulence and CNS pathology
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Jenny K. Stodola, Guillaume Dubois, Alain Le Coupanec, Marc Desforges, Pierre J. Talbot The OC43 strain of human coronavirus (HCoV-OC43) is an ubiquitous respiratory tract pathogen possessing neurotropic capacities. Coronavirus structural envelope (E) protein possesses specific motifs involved in protein-protein interaction or in homo-oligomeric ion channel formation, which are known to play various roles including in virion morphology/assembly and in cell response to infection and/or virulence. Making use of recombinant viruses either devoid of the E protein or harboring mutations either in putative transmembrane domain or PDZ-binding motif, we demonstrated that a fully functional HCoV-OC43 E protein is first needed for optimal production of recombinant infectious viruses. Furthermore, HCoV-OC43 infection of human epithelial and neuronal cell lines, of mixed murine primary cultures from the central nervous system and of mouse central nervous system showed that the E protein is critical for efficient and optimal virus replication and propagation, and thereby for neurovirulence.
February 2018
Inhibition of type I interferon responses by adenovirus serotype-dependent Gas6 binding
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Natalie F. Nidetz, Tom M. Gallagher, Christopher M. Wiethoff The clinical use of many adenovirus vaccine vectors (AdVs) is limited by the presence of pre-existing antibodies in human populations, which prevent common AdVs from transducing cells and expressing immunogenic gene products. Rare serotype AdVs, such as HAdV-28D can bypass pre-existing immunity. However, rare AdVs stimulate high-levels of type I interferon (IFN), which suppresses antigenic gene expression and therefore limits immunogenicity. Recent studies identified Gas6 as a factor that connects enveloped viruses to host-cell receptor tyrosine kinases, in turn generating signaling cascades that antagonize type I IFN responses. We discovered that Gas6 bound to the fiber proteins of common AdV serotypes, such as HAdV-5C, with a higher affinity than rare HAd-28D fibers. AdV-associated Gas6 suppressed IFN production by common AdVs and enhanced long-term expression of AdV encoded genes. We hypothesize that rare AdV serotypes might be engineered to include Gas6 binding motifs, thereby generating novel vectors that are more effective.
February 2018
Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Hui Hui Wong, To Sing Fung, Shouguo Fang, Mei Huang, My Tra Le, Ding Xiang Liu Severe acute respiratory syndrome coronavirus (SARS-CoV) is an inefficient inducer of interferon (IFN) response. It expresses various proteins that effectively circumvent IFN production at different levels via distinct mechanisms. Through the construction of recombinant IBV expressing proteins 8a, 8b and 8ab encoded by SARS-CoV ORF8, we demonstrate that expression of 8b and 8ab enables the corresponding recombinant viruses to partially overcome the inhibitory actions of IFN activation to achieve higher replication efficiencies in cells. We also found that proteins 8b and 8ab could physically interact with IRF3. Overexpression of 8b and 8ab resulted in the reduction of poly (I:C)-induced IRF3 dimerization and inhibition of the IFN-
February 2018
Protein S and Gas6 induce efferocytosis of HIV-1-infected cells
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Bernadette Anne Chua, Jamie Ann Ngo, Kathy Situ, Christina M. Ramirez, Haruko Nakano, Kouki Morizono Efferocytosis, the phagocytic clearance of apoptotic cells, can provide host protection against certain types of viruses by mediating phagocytic clearance of infected cells undergoing apoptosis. It is known that HIV-1 induces apoptosis and HIV-1-infected cells are efferocytosed by macrophages, although its molecular mechanisms are unknown. To elucidate the roles that efferocytosis of HIV-1-infected cells play in clearance of infected cells, we sought to identify molecules that mediate these processes. We found that protein S, present in human serum, and its homologue, Gas6, can mediate phagocytosis of HIV-1-infected cells by bridging receptor tyrosine kinase Mer, expressed on macrophages, to phosphatidylserine exposed on infected cells. Efferocytosis of live infected cells was less efficient than dead infected cells; however, a significant fraction of live infected cells were phagocytosed over 12h. Our results suggest that efferocytosis not only removes dead cells, but may also contribute to macrophage removal of live virus producing cells.
February 2018
The Zika virus envelope protein glycan loop regulates virion antigenicity
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Leslie Goo, Christina R. DeMaso, Rebecca S. Pelc, Julie E. Ledgerwood, Barney S. Graham, Richard J. Kuhn, Theodore C. Pierson Because antibodies are an important component of flavivirus immunity, understanding the antigenic structure of flaviviruses is critical. Compared to dengue virus (DENV), the loop containing the single N-linked glycosylation site on Zika virus (ZIKV) envelope (E) proteins extends further towards the DII fusion loop (DII-FL) on neighboring E proteins within E dimers on mature viruses. Although ZIKV is poorly neutralized by DII-FL antibodies, we demonstrated significantly increased neutralization sensitivity of ZIKV particles incorporating the DENV glycan loop. Increased neutralization sensitivity was independent of E protein glycosylation: ZIKV lacking E protein glycans remained poorly neutralized, whereas ZIKV loop chimeras with or without an E protein glycan were potently neutralized. ZIKV particles lacking the E protein glycan were capable of infecting Raji cells expressing the lectin DC-SIGNR, suggesting the prM glycan of partially mature particles can facilitate entry. Our study provides insight into the determinants of ZIKV E protein function and antigenicity.
February 2018
B23/nucleophosmin interacts with bovine immunodeficiency virus Rev protein and facilitates viral replication
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Ana Maria Passos-Castilho, Claude Marchand, Denis Archambault The bovine immunodeficiency virus (BIV) Rev shuttling protein contains nuclear/nucleolar localization signals and nuclear import/export mechanisms that are novel among lentivirus Rev proteins. Several viral proteins localize to the nucleolus, which may play a role in processes that are essential to the outcome of viral replication. Although BIV Rev localizes to the nucleoli of transfected/infected cells and colocalizes with one of its major proteins, nucleophosmin (NPM1, also known as B23), the role of the nucleolus and B23 in BIV replication remains to be determined. Here, we demonstrate for the first time that BIV Rev interacts with nucleolar phosphoprotein B23 in cells. Using small interfering RNA (siRNA) technology, we show that depletion of B23 expression inhibits virus production by BIV-infected cells, indicating that B23 plays an important role in BIV replication. The interaction between Rev and B23 may represent a potential new target for the development of antiviral drugs against lentiviruses.
February 2018
The genome sequence of Escherichia coli tailed phage D6 and the diversity of Enterobacteriales circular plasmid prophages
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Eddie B. Gilcrease, Sherwood R. Casjens The temperate Escherichia coli bacteriophage D6 can exist as a circular plasmid prophage, and we report here its 91,159bp complete genome sequence. It is a distant relative of the well-studied phage P1, but it is sufficiently different that it typifies a previously undescribed tailed phage type or cluster. Examination of the database of bacterial genome sequences revealed that phage P1 and D6 prophage plasmids are common in the Enterobacteriales, and in addition, previously described Salmonella phage SSU5 represents a different type of temperate tailed phage with a circular plasmid prophage that is also very common in this host order. This analysis also discovered additional divergent clusters of putative circular plasmid prophages within the two larger P1 and SSU5 groups (superclusters) that inhabit the Enterobacteriales as well as bacteria in several other orders in the Gamma-proteobacteria class. Very few of these sequences are annotated as putative prophages.
February 2018
Phage T4 endonuclease SegD that is similar to group I intron endonucleases does not initiate homing of its own gene
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Andrey S. Sokolov, Oleg R. Latypov, Peter M. Kolosov, Michael G. Shlyapnikov, Tamara A. Bezlepkina, Natalia S. Kholod, Farid A. Kadyrov, Igor E. Granovsky Homing endonucleases are a group of site-specific endonucleases that initiate homing, a nonreciprocal transfer of its own gene into a new allele lacking this gene. This work describes a novel phage T4 endonuclease, SegD, which is homologous to the GIY-YIG family of homing endonucleases. Like other T4 homing endonucleases SegD recognizes an extended, 16bp long, site, cleaves it asymmetrically to form 3
February 2018
Structure-function insights into chikungunya virus capsid protein: Small molecules targeting capsid hydrophobic pocket
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Rajesh Sharma, Pooja Kesari, Pravindra Kumar, Shailly Tomar The crystal structure of chikungunya (CHIKV) virus capsid protease domain has been determined at 2.2
February 2018
Phylogenetic analysis reveals three distinct epidemiological profiles in Dutch and Flemish blood donors with hepatitis B virus infection
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Thijs J. van de Laar, V
February 2018
Ross River virus envelope glycans contribute to disease through activation of the host complement system
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Bronwyn M. Gunn, Jennifer E. Jones, Reed S. Shabman, Alan C. Whitmore, Sanjay Sarkar, Lance K. Blevins, Thomas E. Morrison, Mark T. Heise Mannose binding lectin (MBL) generally plays a protective role during viral infection, yet MBL-mediated complement activation promotes Ross River virus (RRV)-induced inflammatory tissue destruction, contributing to arthritis and myositis. As MBL binds to carbohydrates, we hypothesized that N-linked glycans on the RRV envelope glycoproteins act as ligands for MBL. Using a panel of RRV mutants lacking the envelope N-linked glycans, we found that MBL deposition onto infected cells was dependent on the E2 glycans. Moreover, the glycan-deficient viruses exhibited reduced disease and tissue damage in a mouse model of RRV-induced myositis compared to wild-type RRV, despite similar viral load and inflammatory infiltrates within the skeletal muscle. Instead, the reduced disease induced by glycan-deficient viruses was linked to decreased MBL deposition and complement activation within inflamed tissues. These results demonstrate that the viral N-linked glycans promote MBL deposition and complement activation onto RRV-infected cells, contributing to the development of RRV-induced myositis.
15 January 2018
Zika viral infection and neutralizing human antibody response in a BLT humanized mouse model
Publication date: February 2018
Source:Virology, Volume 515 Author(s): Kimberly Schmitt, Paige Charlins, Milena Veselinovic, Lauren Kinner-Bibeau, Shuang Hu, James Curlin, Leila Remling-Mulder, Ken E. Olson, Tawfik Aboellail, Ramesh Akkina Many murine and non-human primate animal models have been recently developed to understand Zika viral pathogenesis. However, a major limitation with these models is the inability to directly examine the human-specific immune response. Here, we utilized a BLT humanized mouse model endowed with a transplanted human immune system. Plasma viremia could be detected within 48h after viral challenge and viremia persisted for as long as 220 days in some mice. Neutralizing human antibody was detected in infected mice and mouse sera showed reactivity with the viral envelope and capsid proteins in a radio-immunoprecipitation assay. Human monocytes/macrophages, B cells and hematopoietic stem cells in the bone marrow were found to be virus infected. These data establish that BLT mice are permissive for Zika viral infection and are capable of generating viral-specific human immune responses thus providing a human surrogate model for future testing of vaccine and antiviral therapeutic candidates.
15 January 2018
Editorial Board
Publication date: 15 January 2018
Source:Virology, Volume 514

15 January 2018
The roles of five conserved lentiviral RNA structures in HIV-1 replication
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Yang Liu, Jianbo Chen, Olga A. Nikolaitchik, Belete A. Desimmie, Steven Busan, Vinay K. Pathak, Kevin M. Weeks, Wei-Shau Hu The HIV-1 RNA genome contains complex structures with many structural elements playing regulatory roles during viral replication. A recent study has identified multiple RNA structures with unknown functions that are conserved among HIV-1 and two simian immunodeficiency viruses. To explore the roles of these conserved RNA structures, we introduced synonymous mutations into the HIV-1 genome to disrupt each structure. These mutants exhibited similar particle production, viral infectivity, and replication kinetics relative to the parent NL4-3 virus. However, when replicating in direct competition with the wild-type NL4-3 virus, mutations of RNA structures at inter-protein domain junctions can cause fitness defects. These findings reveal the ability of HIV-1 to tolerate changes in its sequences, even in apparently highly conserved structures, which permits high genetic diversity in HIV-1 population. Our results also suggest that some conserved RNA structures may function to fine-tune viral replication.
15 January 2018
Retargeted and detargeted adenovirus for gene delivery to the muscle
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Tien V. Nguyen, Stephanie S. Anguiano-Zarate, William E. Matchett, Mary E. Barry, Michael A. Barry We previously selected muscle binding peptides 12.51 and 12.52 from "context-specific" phage display libraries for introduction into adenovirus (Ad) vectors. In this work, these peptides were inserted into the hypervariable region (HVR) 5 loop of the Ad5 hexon protein to display 720 peptides per virions. HVR-12.51 and 12.52 increased transduction of C2C12 cells up to 20-fold when compared to unmodified Ad5. 12.51 increased in vivo muscle transduction 2 to 7-fold over unmodified Ad after intramuscular injection in mice and hamsters. 12.52 did not increase muscle transduction. Notably, insertion of 12.51 into the hexon reduced liver transduction 80-fold when compared to unmodified Ad5 after intravenous injection. Increased muscle transduction in mice translated into increased immune responses after gene-based vaccination. These data suggest there are merits to retargeting and detargeting benefits to modifying the hexons of Ads with peptide ligands.
15 January 2018
Increases in the competitive fitness of West Nile virus isolates after introduction into California
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Gabriella Worwa, Andra A. Hutton, Mich
15 January 2018
Discovery of novel anelloviruses in small mammals expands the host range and diversity of the Anelloviridae
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): William Marciel de Souza, Marc
15 January 2018
Rab1A is required for assembly of classical swine fever virus particle
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Jihui Lin, Chengbao Wang, Wulong Liang, Jing Zhang, Longxiang Zhang, Huifang Lv, Wang Dong, Yanming Zhang Rab1A belongs to the small Rab GTPase family and is involved in the lifecycle of numerous viruses. Here, knockdown of Rab1A inhibited CSFV growth. Further study revealed that Rab1A depletion decreased intracellular and extracellular CSFV titers, but did not affect intracellular virus genome copies and E2 protein expression within a virus lifecycle, which suggested that Rab1A is required for CSFV particle assembly rather than for genome replication or virion release. This was proofed by blocking the spread of virus using neutralizing antibodies, through which the negative effects of Rab1A knockdown on multi-cycle replication of CSFV were eliminated. Moreover, co-immunoprecipitation and confocal microscopy assays showed that Rab1A bound to CSFV NS5A protein, indicating that Rab1A and viral NS5A proteins may work cooperatively during CSFV particle assembly. In conclusion, this study demonstrated for the first time that Rab1A is required for CSFV particle assembly and binds to viral particle assembly-related NS5A protein.
15 January 2018
Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Ahmed Atef Mesalam, Isabelle Desombere, Ali Farhoudi, Freya Van Houtte, Lieven Verhoye, Jonathan Ball, Jean Dubuisson, Steven K.H. Foung, Arvind H. Patel, Mats A.A. Persson, Geert Leroux-Roels, Philip Meuleman Monoclonal antibodies (mAbs) targeting the hepatitis C virus (HCV) envelope have been raised mainly against envelope protein 2 (E2), while the antigenic epitopes of envelope protein 1 (E1) are not fully identified. Here we describe the detailed characterization of a human mAb, designated A6, generated from an HCV genotype 1b infected patient. ELISA results showed reactivity of mAb A6 to full-length HCV E1E2 of genotypes 1a, 1b and 2a. Epitope mapping identified a region spanning amino acids 230239 within the N-terminal region of E1 as critical for binding. Antibody binding to this epitope was not conformation dependent. Neutralization assays showed that mAb A6 lacks neutralizing capacity and does not interfere with the activity of known neutralizing antibodies. In summary, mAb A6 is an important tool to study the structure and function of E1 within the viral envelope, a crucial step in the development of an effective prophylactic HCV vaccine.
15 January 2018
Wheat streak mosaic virus coat protein is a determinant for vector transmission by the wheat curl mite
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Satyanarayana Tatineni, Anthony J. McMechan, Gary L. Hein Wheat streak mosaic virus (WSMV; genus Tritimovirus; family Potyviridae), is transmitted by the wheat curl mite (Aceria tosichella Keifer). The requirement of coat protein (CP) for WSMV transmission by the wheat curl mite was examined using a series of viable deletion and point mutations. Mite transmission of WSMV was completely abolished with deletions comprising CP amino acids 58100. In contrast, the amino-proximal (amino acids 627 and 3657) and carboxy-terminal (14 amino acids) regions of CP were expendable for mite transmission. Mutation of aspartic acid residues at amino acid positions 289 or 326 (D289A or D326A) at the carboxy-proximal region of CP significantly reduced mite transmission. Remarkably, every wheat plant infected by mutants D289A or D326A through mite transmission but not with in vitro transcripts contained a second-site mutation of R131C and N275H, respectively. Collectively, these data demonstrate for the first time that CP is a determinant for an eriophyid-transmitted plant virus.
15 January 2018
Lethal murine infection model for human respiratory disease-associated Pteropine orthoreovirus
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Yuta Kanai, Takahiro Kawagishi, Minoru Okamoto, Yusuke Sakai, Yoshiharu Matsuura, Takeshi Kobayashi Pteropine orthoreovirus (PRV) is an emerging bat-borne human pathogen causing severe respiratory illness. To date, however, the evaluation of PRV virulence has largely depended on the limited numbers of clinical cases owing to the lack of animal models. To develop an in vivo model of PRV infection, an inbred C3H mouse strain was infected intranasally with pathogenic PRV strain Miyazaki-Bali/2007. C3H mice suffered severe lung infection with significant body weight reduction and died within 7 days after intranasal infection. Infectious viruses were isolated mainly from the lungs and trachea. Histopathological examination revealed interstitial pneumonia with monocytes infiltration. Following repeated intranasal infection, mice developed antibodies to particular structural and non-structural proteins of PRV. The results of these immunological assays will help to develop laboratory protocols for sero-epidemiological studies. Our small rodent model of lethal respiratory infection will further allow investigation of the molecular mechanisms underlying the high pathogenicity of PRV.
15 January 2018
Male Syrian hamsters are more susceptible to intravenous infection with species C human adenoviruses than are females
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Baoling Ying, Jacqueline F. Spencer, Ann E. Tollefson, William S.M. Wold, Karoly Toth Recently, increasing attention has been focused on the influence of sex on the course of infectious diseases. Thus far, the best-documented examples point toward an immune-mediated mechanism: the generally stronger immune response in females can result in a faster clearance of the pathogen or, conversely, a more severe immune-mediated pathology. Here, we report that human species C adenoviruses replicate more and cause more pathology in male Syrian hamsters than in females. We also show that this sex disparity is not caused by a stronger immune response to the infection by the female hamsters. Rather, the liver of male hamsters is more susceptible to adenovirus infection: after intravenous injection, more hepatocytes become infected in male animals than in females. We hypothesize that Kupffer cells (hepatic tissue macrophages) of female animals are more active in sequestering circulating virions, and thus protect hepatocytes more efficiently than those of males.
15 January 2018
The antimicrobial peptide HS-1 inhibits dengue virus infection
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Juliana M.C. Monteiro, Michelle D. Oliveira, Roberto S. Dias, Lorena Nacif-Mar
15 January 2018
Extensive diversity and evolution of hepadnaviruses in bats in China
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Fang-Yuan Nie, Xian-Dan Lin, Zong-Yu Hao, Xiao-Nan Chen, Zhao-Xiao Wang, Miao-Ruo Wang, Jun Wu, Hong-Wei Wang, Guoqiang Zhao, Runlin Z. Ma, Edward C. Holmes, Yong-Zhen Zhang To better understand the evolution of hepadnaviruses, we sampled bats from Guizhou, Henan and Zhejiang provinces, China, and rodents from Zhejiang province. Genetically diverse hepadnaviruses were identified in a broad range of bat species, with an overall prevalence of 13.3%. In contrast, no rodent hepadnaviruses were identified. The newly discovered bat hepadnaviruses fell into two distinct phylogenetic groups. The viruses within the first group exhibited high diversity, with some closely related to viruses previously identified in Yunnan province. Strikingly, the newly discovered viruses sampled from Jiyuan city in the second phylogenetic group were most closely related to those found in bats from West Africa, suggestive of a long-term association between bats and hepadnaviruses. A co-phylogenetic analysis revealed frequent cross-species transmission among bats from different species, genera, and families. Overall, these data suggest that there are likely few barriers to the cross-species transmission of bat hepadnaviruses.
15 January 2018
Saliva of Ixodes ricinus enhances TBE virus replication in dendritic cells by modulation of pro-survival Akt pathway
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Jaroslava Lieskovsk
15 January 2018
Increased surface expression of HIV-1 envelope is associated with improved antibody response in vaccinia prime/protein boost immunization
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Michael J. Hogan, Angela Conde-Motter, Andrea P.O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, Drew Weissman HIV-1 envelope (Env)-based vaccines have so far largely failed to induce antibodies that prevent HIV-1 infection. One factor proposed to limit the immunogenicity of cell-associated Env is its low level of expression on the cell surface, restricting accessibility to antibodies. Using a vaccinia prime/protein boost protocol in mice, we explored the immunologic effects of mutations in the Env cytoplasmic tail (CT) that increased surface expression, including partial truncation and ablation of a tyrosine-dependent endocytosis motif. After vaccinia primes, CT-modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers, although results were variable between isolates. These data indicate that the immunogenicity of HIV-1 Env in a prime/boost vaccine can be enhanced in a strain-dependent manner by CT mutations that increase Env surface expression, thus highlighting the importance of the prime in this vaccine format.
15 January 2018
Modeling the pathology, immune responses, and kinetics of HSV-1 replication in the lip scarification model
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Kevin P. Egan, Alexander G. Allen, Brian Wigdahl, Stephen R. Jennings The lip scarification model of herpes simplex virus type 1 (HSV-1) infection can be used to study acute infection in the orofacial tissue and the establishment of viral latency. In this study, mice were inoculated with HSV-1 and tissue harvested during the acute phase of infection. Clinical presentation of classical open sores on the lip of infected mice was observed. We defined the histopathology, disease scores, and immune infiltration of the lower lip during the formation and resolution of the clinical lesions. Finally, the kinetics of virus replication and transport of viral genomes to the trigeminal ganglia were established. With the virological and pathologic events of acute infection defined, the HSV-1 lip scarification model can now be used to study primary HSV-1 infection, invasion of the trigeminal ganglia, and establishment of latency.

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15 January 2018
Establishment of robust HCV genotype 4d, 5a, and 6a replicon systems
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Gregory Camus, Simin Xu, Bin Han, Julia Lu, Hadas Dvory-Sobol, Mei Yu, Guofeng Cheng, Michael D. Miller, Brian P. Doehle, Hongmei Mo Hepatitis C Virus (HCV) is a diverse human pathogen which displays ~15% divergence at the subtype level. To facilitate development of antivirals with pan-genotype activity, we developed the first genotype 4d subgenomic replicon, as well as new replicons for genotypes 5a, and 6a. Adaptive mutations developed in these replicons differ greatly across genotypes. Their impacts on the replication capacity were tested using site-directed mutants. In the genotype 4d replicon, single mutations have moderate effect, but the double mutation NS4A-Q34R+NS5A-S232G increased the replication capacity by 161-fold. These new stable replicon cell lines were used to determine the antiviral activity of HCV inhibitors. The NS3 protease inhibitor voxilaprevir, NS5A second generation inhibitor velpatasvir, and NS5B nucleoside analog inhibitor sofosbuvir, had similar antiviral activities across the different genotypes/subtypes tested, while the NS5A first generation inhibitor, ledipasvir, had very good antiviral activity against GT1, 4, 5, and 6 in vitro.
15 January 2018
Nuclear myosin 1 associates with papillomavirus E2 regulatory protein and influences viral replication
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Eve Sankovski, Aare Abroi, Mart Ustav, Mart Ustav Nuclear myosin 1c (NM1) associates with RNA polymerases and is a partner in the chromatin remodeling complex B-WICH. This complex, which also contains WSTF and SNF2h proteins, is involved in transcriptional regulation. We report herein that papillomavirus protein E2 binds to NM1 and co-precipitates with the WSTF and SNF2h proteins. Our data suggest that E2 associates with the cellular B-WICH complex through binding to NM1. E2 and NM1 associate via their N-terminal domains and this interaction is ATP dependent. The cellular multifunctional protein Brd4 and beta-actin are also present in the NM1-E2 complex. NM1 downregulation by siRNA increases the replication of the BPV1 and HPV5 genomes but does not affect HPV18 genome replication. These results suggest that the B-WICH complex may play a role in the papillomavirus life cycle through NM1 and E2 protein interaction.
15 January 2018
Molecular evolution and invasion pattern of Cryphonectria hypovirus 1 in Europe: Mutation rate, and selection pressure differ between genome domains
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Jelena Mlinarec, Lucija Nuskern, Marin Je

Structural features of the salivary gland hypertrophy virus of the tsetse fly revealed by cryo-electron microscopy and tomography
Publication date: 15 January 2018
Source:Virology, Volume 514 Author(s): Igor Orlov, Robert Drillien, Dani
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