bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Wolbachia on Replication of West Nile Virus in a Mosquito Cell Line and Adult Mosquitoes
Authors: Hussain Mazhar , Lu Guangjin , Torres Shessy , Edmonds Judith H. , Kay Brian H. , Khromykh Alexander A. , Asgari Sassan 
Published: November 2012

ABSTRACTWolbachiaas an endosymbiont is widespread in insects and other arthropods and is best known for reproductive manipulations of the host. Recently, it has been shown thatwMelpop andwMel strains ofWolbachiainhibit the replication of several RNA viruses, including dengue virus, and other vector-borne pathogens (e.g.,Plasmodiumand filarial nematodes) in mosquitoes, providing an alternative approach to limit the transmission of vector-borne pathogens. In this study, we tested the effect ofWolbachiaon the replication of West Nile Virus (WNV). Surprisingly, accumulation of the genomic RNA of WNV for all three strains of WNV tested (New York 99, Kunjin, and New South Wales) was enhanced inWolbachia-infectedAedes aegypticells (Aag2). However, the amount of secreted virus was significantly reduced in the presence ofWolbachia. Intrathoracic injections showed that replication of WNV inA. aegyptimosquitoes infected withwMel strain ofWolbachiawas not inhibited, whereaswMelPop strain ofWolbachiasignificantly reduced the replication of WNV in mosquitoes. Further, whenwMelPop mosquitoes were orally fed with WNV, virus infection, transmission, and dissemination rates were very low inWolbachia-free mosquitoes and were completely inhibited in the presence ofWolbachia. The results suggest that (i) despite the enhancement of viral genomic RNA replication in theWolbachia-infected cell line the production of secreted virus was significantly inhibited, (ii) the antiviral effect in intrathoracically infected mosquitoes depends on the strain ofWolbachia, and (iii) replication of the virus in orally fed mosquitoes was completely inhibited inwMelPop strain ofWolbachia.
Mapping Viral Functional Domains for Genetic Diversity in Plants
Authors: Pita Justin S. , Roossinck Marilyn J. 
Published: November 2012

ABSTRACT

Cucumber mosaic virus
(CMV) comprises numerous isolates with various levels of in-host diversity. Subgroup-distinctive features of the Fny and LS strains provided us with a platform to genetically map the viral control elements for genetic variation
in planta
. We found that both RNAs 1 and 2 controlled levels of genetic diversity, and further fine mapping revealed that the control elements of mutation frequency reside within the first 596 amino acids (aa) of RNA 1. The 2a/2b overlapping region of the 2a protein also contributed to control of viral genetic variation. Furthermore, the 3′ nontranslated region (NTR) of RNA 3 constituted a hot spot of polymorphism, where the majority of fixed mutations found in the population were clustered. The 2b gene of CMV, a viral suppressor of gene silencing, controls the abundance of the fixed mutants in the viral population via a host-dependent mechanism.
Crystal Structure of the Cowpox Virus-Encoded NKG2D Ligand OMCP
Authors: Lazear Eric , Peterson Lance W. , Nelson Chris A. , Fremont Daved H. 
Published: November 2012

ABSTRACT
The NKG2D receptor is expressed on the surface of NK, T, and macrophage lineage cells and plays an important role in antiviral and antitumor immunity. To evade NKG2D recognition, herpesviruses block the expression of NKG2D ligands on the surface of infected cells using a diverse repertoire of sabotage methods. Cowpox and monkeypox viruses have taken an alternate approach by encoding a soluble NKG2D ligand, the orthopoxvirus major histocompatibility complex (MHC) class I-like protein (OMCP), which can block NKG2D-mediated cytotoxicity. This approach has the advantage of targeting a single conserved receptor instead of numerous host ligands that exhibit significant sequence diversity. Here, we show that OMCP binds the NKG2D homodimer as a monomer and competitively blocks host ligand engagement. We have also determined the 2.25-Å-resolution crystal structure of OMCP from the cowpox virus Brighton Red strain, revealing a truncated MHC class I-like platform domain consisting of a beta sheet flanked with two antiparallel alpha helices. OMCP is generally similar in structure to known host NKG2D ligands but has notable variations in regions typically used to engage NKG2D. Additionally, the determinants responsible for the 14-fold-higher affinity of OMCP for human than for murine NKG2D were mapped to a single loop in the NKG2D ligand-binding pocket.
Epigenetic Silencing of Antiviral Genes Renders Clones of Huh-7 Cells Permissive for Hepatitis C Virus Replication
Authors: Chen Qiuyue , Denard Bray , Huang Hua , Ye Jin 
Published: November 2012

ABSTRACT

Hepatitis C virus (HCV) does not replicate efficiently in wild-type human hepatoma Huh-7 cells, but it replicates robustly in certain subclones of Huh-7 cells. Previously, we demonstrated that silencing of cyclic AMP (cAMP) response element binding protein 3-like 1 (
CREB3L1
), a cellular transcription factor that inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of Huh-7 cells permissive for HCV replication. Here we show that silencing of myxovirus resistant 1 (
MX1
), a known interferon-induced antiviral gene, is responsible for HRP4 cells, another subclone of Huh-7 cells, being permissive for HCV replication. Both
CREB3L1
and
MX1
are epigenetically silenced through DNA methylation in HRP1 and HRP4 cells, respectively. We further demonstrate that Huh-7 cells exist as a mixed population of cells with distinct patterns of gene methylation and HCV replicates in subpopulations of Huh-7 cells that have antiviral genes epigenetically silenced by DNA hypermethylation. Our results demonstrate that understanding the mechanism through which subclones of Huh-7 cells become permissive for HCV replication is crucial for studying their interaction with HCV.
Functional and Structural Characterization of Neutralizing Epitopes of Measles Virus Hemagglutinin Protein
Authors: Tahara Maino , Ito Yuri , Brindley Melinda A. , Ma Xuemin , He Jilan , Xu Songtao , Fukuhara Hideo , Sakai Kouji , Komase Katsuhiro , Rota Paul A. , Plemper Richard K. , Maenaka Katsumi , Takeda Makoto 
Published: November 2012

ABSTRACT

Effective vaccination programs have dramatically reduced the number of measles-related deaths globally. Although all the available data suggest that measles eradication is biologically feasible, a structural and biochemical basis for the single serotype nature of measles virus (MV) remains to be provided. The hemagglutinin (H) protein, which binds to two discrete proteinaceous receptors, is the major neutralizing target. Monoclonal antibodies (MAbs) recognizing distinct epitopes on the H protein were characterized using recombinant MVs encoding the H gene from different MV genotypes. The effects of various mutations on neutralization by MAbs and virus fitness were also analyzed, identifying the location of five epitopes on the H protein structure. Our data in the present study demonstrated that the H protein of MV possesses at least two conserved effective neutralizing epitopes. One, which is a previously recognized epitope, is located near the receptor-binding site (RBS), and thus MAbs that recognize this epitope blocked the receptor binding of the H protein, whereas the other epitope is located at the position distant from the RBS. Thus, a MAb that recognizes this epitope did not inhibit the receptor binding of the H protein, rather interfered with the hemagglutinin-fusion (H-F) interaction. This epitope was suggested to play a key role for formation of a higher order of an H-F protein oligomeric structure. Our data also identified one nonconserved effective neutralizing epitope. The epitope has been masked by an
N
-linked sugar modification in some genotype MV strains. These data would contribute to our understanding of the antigenicity of MV and support the global elimination program of measles.
Comprehensive Mutational Analysis Reveals p6
Gag
Phosphorylation To Be Dispensable for HIV-1 Morphogenesis and Replication
Authors: Radestock Benjamin , Morales Ivonne , Rahman Sheikh Abdul , Radau Sonja , Glass Bärbel , Zahedi René Peiman , Müller Barbara , Kräusslich Hans-Georg 
Published: November 2012

ABSTRACT

The structural polyprotein Gag of human immunodeficiency virus type 1 (HIV-1) is necessary and sufficient for formation of virus-like particles. Its C-terminal p6 domain harbors short peptide motifs that facilitate virus release from the plasma membrane and mediate incorporation of the viral Vpr protein. p6 has been shown to be the major viral phosphoprotein in HIV-1-infected cells and virions, but the sites and functional relevance of p6 phosphorylation are not clear. Here, we identified phosphorylation of several serine and threonine residues in p6 in purified virus preparations using mass spectrometry. Mutation of individual candidate phosphoacceptor residues had no detectable effect on virus assembly, release, and infectivity, however, suggesting that phosphorylation of single residues may not be functionally relevant. Therefore, a comprehensive mutational analysis was conducted changing all potentially phosphorylatable amino acids in p6, except for a threonine that is part of an essential peptide motif. To avoid confounding changes in the overlapping
pol
reading frame, mutagenesis was performed in a provirus with genetically uncoupled
gag
and
pol
reading frames. An HIV-1 derivative carrying 12 amino acid changes in its p6 region, abolishing all but one potential phosphoacceptor site, showed no impairment of Gag assembly and virus release and displayed only very subtle deficiencies in viral infectivity in T-cell lines and primary lymphocytes. All mutations were stable over 2 weeks of culture in primary cells. Based on these findings, we conclude that phosphorylation of p6 is dispensable for HIV-1 assembly, release, and infectivity in tissue culture.
Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus
Authors: Carter Donald M. , Bloom Chalise E. , Nascimento Eduardo J. M. , Marques Ernesto T. A. , Craigo Jodi K. , Cherry Joshua L. , Lipman David J. , Ross Ted M. 
Published: November 2012

ABSTRACT
Individuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses.
Stress Granule Formation Induced by Measles Virus Is Protein Kinase PKR Dependent and Impaired by RNA Adenosine Deaminase ADAR1
Authors: Okonski Kristina M. , Samuel Charles E. 
Published: November 2012

ABSTRACT

ADAR1, an interferon (IFN)-inducible double-stranded (ds) RNA-specific adenosine deaminase, downregulates host innate responses, including activation of the dsRNA-dependent protein kinase (PKR) and induction of IFN-β mRNA. Conversely, PKR amplifies IFN-β induction by measles virus (MV) and inhibits virus protein synthesis. Formation of stress granules (SGs), cytoplasmic aggregates of stalled translation complexes and RNA-binding proteins, is a host response to virus infection mediated by translation initiation factor eIF2α phosphorylation. We examined the roles of PKR and ADAR1 in SG formation using HeLa cells stably deficient in either PKR (PKR
kd
) or ADAR1 (ADAR1
kd
) compared to control (CON
kd
) cells. Infection with either wild-type (WT) MV or an isogenic mutant lacking C protein expression (C
ko
) comparably induced formation of SG in ADAR1
kd
cells, whereas only the C
ko
mutant was an efficient inducer in control cells. Both ADAR1 and PKR colocalized with SG following infection. MV-induced; SG formation was PKR dependent but impaired by ADAR1. Complementation of ADAR1
kd
cells by expression of either p150 WT isoform or the p150 Zα (Y177A) Z-DNA-binding mutant of ADAR1 restored suppression of host responses, including SG formation and PKR activation. In contrast, neither the p110 WT isoform nor the p150 catalytic (H910A, E912A) mutant of ADAR1 complemented the ADAR1
kd
phenotype. These results further establish ADAR1 as a suppressor of host innate responses, including activation of PKR and the subsequent SG response.
Complete Genome Analysis of Three Live Attenuated Rinderpest Virus Vaccine Strains Derived through Serial Passages in Different Culture Systems
Authors: Jeoung Hye-Young , Lee Myoung-Heon , Yeh Jung-Yong , Lim Ji-Ae , Lim Seong-in , Oem Jae-Ku , Song Jae-Young , Lee Won-Ha , Park Jong-Hwan , An Dong-Jun 
Published: November 2012

ABSTRACT

The genomes of three South Korean Rinderpest virus vaccine strains (L72, LA77, and LA96) were analyzed in order to investigate their genetic variability. These three vaccine strains were all derived from the same virus strain origin (Fusan) through repeated passages in different culture systems. The full genome length of the three strains was 15,882 nucleotides, and the sequence similarity between the three South Korean RPV strains at the nucleotide level was 98.1 to 98.9%. The genetic distance between Nakamura III, L72, LA77, LA96, and LATC06 and the Kabete strain was greater than that between the Fusan and Kabete strains for the P, V, and C genes. The difference in pathogenicity among these strains might be due to the V gene, which has a positive (>1) selection ratio based on the analysis of synonymous (
dS
) and nonsynonymous (
dN
) substitution rates (
dN
/
dS
ratio [ω]).
Minimum Requirements for Bluetongue Virus Primary Replication
In Vivo
Authors: Matsuo Eiko , Roy Polly 
Published: November 2012

ABSTRACT

The replication mechanism of bluetongue virus (BTV) has been studied by an
in vivo
reverse genetics (RG) system identifying the importance of certain BTV proteins for primary replication of the virus. However, a unique
in vitro
cell-free virus assembly system was subsequently developed, showing that it did not require the same set of viral components, which is indicative of differences in these two systems. Here, we studied the
in vivo
primary replicase complex more in-depth to determine the minimum components of the complex. We showed that while NS2 is an essential component of the primary replication stage during BTV infection, NS1 is not an essential component but may play a role in enhancing BTV protein synthesis. Furthermore, we demonstrated that VP7, a major structural protein of the inner core, is not required for primary replication but appears to stabilize the replicase complex. In contrast, VP3, the other major structural core protein, is an essential component of the complex, together with the three minor enzymatic proteins (VP1, VP4, and VP6) of the core. In addition, our data have demonstrated that the smallest minor protein, VP6, which is known to possess an RNA-dependent helicase activity, may also act as an RNA translocator during assembly of the primary replicase complex.
In Vitro
and
In Vivo
Isolation of a Novel Rearranged Porcine Circovirus Type 2
Authors: Wen Libin , He Kongwang , Li Bin , Wang Xiaomin , Guo Rong li , Yu Zhengyu , Mao Aihua , Ni Yanxiu , Zhang Xuehan , Zhou Junming , Lv Lixin , Jiang Jieyuan 
Published: November 2012

ABSTRACT

Here, we present the first report of a novel rearranged porcine circovirus type 2 (PCV2) strain named BIV, isolated from both
in vitro
and
in vivo
sources. The complete circular genome of BIV is 896 nucleotides in length. The data will help us to update current knowledge of the replication of PCV2 viruses in cell culture and of their molecular evolution, as well as their diagnosis.
Complete Genome Sequence of Hepatitis E Virus from Rabbits in the United States
Authors: Cossaboom Caitlin M. , Córdoba Laura , Cao Dianjun , Ni Yan-Yan , Meng Xiang-Jin 
Published: November 2012

ABSTRACT

Hepatitis E virus (HEV) is a single-strand positive-sense RNA virus in the family
Hepeviridae
. The disease caused by HEV, hepatitis E, is an important public health problem in developing countries of Asia and Africa and is also endemic in many industrialized countries, including the United States. HEV has been identified from several other animal species in addition to humans, including the pig, chicken, mongoose, deer, rabbit, ferret, bat, and fish. Here we report the complete genome sequence of the first strain of HEV from rabbits in the United States. Sequence and phylogenetic analyses revealed that the U.S. rabbit HEV is a distant member of the zoonotic genotype 3 HEV, thus raising a concern for potential zoonotic human infection. A unique 90-nucleotide insertion within the X domain of the ORF1 was identified in the rabbit HEV, and this insertion may play a role in the species tropism of HEV.
Antiviral Therapy Can Reverse the Development of Immune Senescence in Elderly Mice with Latent Cytomegalovirus Infection
Authors: Beswick Mark , Pachnio Annette , Lauder Sarah N. , Sweet Clive , Moss Paul A. 
Published: November 2012

ABSTRACT

Cytomegalovirus (CMV) infection leads to the development of adaptive and humoral immune responses that are among the largest for any pathogen, and intriguingly, the magnitude of the immune response increases with age, a phenomenon termed “memory inflation.” Elevated CMV-specific immunity has been correlated with an increased mortality rate in elderly individuals and with impaired vaccination responses. The latent phase of CMV infection is characterized by intermittent episodes of subclinical viral reactivation and the production of immunogenic transcripts that may maintain memory inflation of virus-specific cytotoxic lymphocytes. However, the relative importance of CMV reactivation in the development of memory inflation is uncertain, as is the potential for antiviral treatment to reverse this effect. Here, we administered valaciclovir for up to 12 months in mice with established murine CMV (MCMV) infection. Treatment reduced the magnitude of the MCMV-specific CD8
+
T-lymphocyte response by 80%, and the residual MCMV tetramer-specific lymphocytes exhibited a less differentiated phenotype. In addition, latent MCMV infection suppressed the proportion of naïve CD8
+
T cells by 60% compared to antiviral-treated mice or MCMV-negative animals. Furthermore, treatment led to a reduction in influenza A viral loads following a challenge in elderly MCMV-infected animals and also reduced the differentiation of influenza virus-specific cytotoxic lymphocytes. These observations demonstrate that MCMV-specific memory inflation is maintained by viral replication and that therapeutic intervention could lead to improved immune function.
Complete Genome Sequence of an Enterovirus 80 Strain Isolated in China
Authors: Tao Zexin , Cui Ning , Liu Guifang , Chen Peng , Xu Aiqiang , Song Lizhi , Ji Feng , Wang Haiyan , Song Yanyan 
Published: November 2012

ABSTRACT

Enterovirus 80 (EV80) is a newly identified serotype of the species
Human enterovirus B
. An EV80 strain designated HZ01/SD/CHN/2004 was isolated from an acute flaccid paralysis case in Shandong, China, in 2004. Complete genome comparison revealed 79.5% similarity with the prototype strain and an insertion of 36 nucleotides in the 3′ end of the VP1 coding region. Intertypic recombination with other serotypes was observed. This is the first report of the complete genome of EV80 in China.
Complete Genome Sequence Analysis of a Duck Circovirus from Guangxi Pockmark Ducks
Authors: Xie Liji , Xie Zhixun , Zhao Guangyuan , Liu Jiabo , Pang Yaoshan , Deng Xianwen , Xie Zhiqin , Fan Qing 
Published: November 2012

ABSTRACT

We report here the complete genomic sequence of a novel duck circovirus (DuCV) strain, GX1104, isolated from Guangxi pockmark ducks in Guangxi, China. The whole nucleotide sequence had the highest homology (97.2%) with the sequence of strain TC/2002 (GenBank accession number
AY394721.1
) and had a low homology (76.8% to 78.6%) with the sequences of other strains isolated from China, Germany, and the United States. This report will help to understand the epidemiology and molecular characteristics of Guangxi pockmark duck circovirus in southern China.
Genome Sequence of a Monoreassortant H1N1 Swine Influenza Virus Isolated from a Pig in Hungary
Authors: Bányai Krisztián , Kovács Eszter , Tóth Ádám György , Biksi Imre , Szentpáli-Gavallér Katalin , Bálint Ádám , Dencső László , Dán Ádám 
Published: November 2012

ABSTRACT
The genome of a porcine H1N1 influenza A strain is reported in this study. The strain proved to be a monoreassortant strain with a typical porcine N1 gene on the genetic backbone of the pandemic H1N1 influenza A virus strain. Monitoring of descendants of the pandemic 2009 H1N1 strain is needed because of concerns that more-virulent strains may emerge in forthcoming epidemic seasons.
Complete Genome Sequence of Vibrio parahaemolyticus Bacteriophage vB_VpaM_MAR
Authors: Alanis Villa Argentina , Kropinski Andrew M. , Abbasifar Reza , Griffiths Mansel W. 
Published: November 2012

ABSTRACT

Vibrio parahaemolyticus
is a major pathogen that is mainly associated with seafood and is a global food safety issue. Our objective was to isolate and completely sequence a specific phage against this bacterium. Phage vB_VpaM_MAR is able to lyse 76% of the
V. parahaemolyticus
strains tested. MAR belongs to the
Myoviridae
family and has a genome comprised of double-stranded DNA with a size of 41,351 bp, a G+C content of 51.3%, and 62 open reading frames (ORFs). Bioinformatic analysis showed that phage MAR is closely related to
Vibrio
phages VHML, VP58.5, and VP882 and
Halomonas aquamarina
phage ΦHAP-1.
Complete Genomic Sequence of a Muscovy Duck-Origin Reticuloendotheliosis Virus from China
Authors: Jiang Tiantian , Lu Xinhao , Yuan Yuan , Zheng Lisha , Shi Jiajian , Zhang Dabing 
Published: November 2012

ABSTRACT
The complete proviral sequence of a Muscovy duck-origin reticuloendotheliosis virus (REV) associated with spontaneously occurring neoplastic disease in 2011 in Zhejiang province, China, was determined. Comparative sequence analyses indicate that the present REV is most closely related to the chicken-origin REV isolate HLJR0901 and the goose-origin isolate Goose/3410/06. These findings suggest that chickens or geese may transmit the REV to Muscovy ducks.