bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-Glycans on the Nipah Virus Attachment Glycoprotein Modulate Fusion and Viral Entry as They Protect against Antibody Neutralization
Authors: Biering Scott B. , Huang Andrew , Vu Andy T. , Robinson Lindsey R. , Bradel-Tretheway Birgit , Choi Eric , Lee Benhur , Aguilar Hector C. 
Published: August 2012

ABSTRACTNipah virus (NiV) is the deadliest known paramyxovirus. Membrane fusion is essential for NiV entry into host cells and for the virus' pathological induction of cell-cell fusion (syncytia). The mechanism by which the attachment glycoprotein (G), upon binding to the cell receptors ephrinB2 or ephrinB3, triggers the fusion glycoprotein (F) to execute membrane fusion is largely unknown. N-glycans on paramyxovirus glycoproteins are generally required for proper protein conformational integrity, transport, and sometimes biological functions. We made conservative mutations (Asn to Gln) at the seven potential N-glycosylation sites in the NiV G ectodomain (G1 to G7) individually or in combination. Six of the seven N-glycosylation sites were found to be glycosylated. Moreover, pseudotyped virions carrying these N-glycan mutants had increased antibody neutralization sensitivities. Interestingly, our results revealed hyperfusogenic and hypofusogenic phenotypes for mutants that bound ephrinB2 at wild-type levels, and the mutant's cell-cell fusion phenotypes generally correlated to viral entry levels. In addition, when removing multiple N-glycans simultaneously, we observed synergistic or dominant-negative membrane fusion phenotypes. Interestingly, our data indicated that 4- to 6-fold increases in fusogenicity resulted from multiple mechanisms, including but not restricted to the increase of F triggering. Altogether, our results suggest that NiV-G N-glycans play a role in shielding virions against antibody neutralization, while modulating cell-cell fusion and viral entry via multiple mechanisms.
Biochemical, Conformational, and Immunogenic Analysis of Soluble Trimeric Forms of Henipavirus Fusion Glycoproteins
Authors: Chan Yee-Peng , Lu Min , Dutta Somnath , Yan Lianying , Barr Jennifer , Flora Michael , Feng Yan-Ru , Xu Kai , Nikolov Dimitar B. , Wang Lin-Fa , Skiniotis Georgios , Broder Christopher C. 
Published: August 2012

ABSTRACT

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are paramyxoviruses discovered in the mid- to late 1990s that possess a broad host tropism and are known to cause severe and often fatal disease in both humans and animals. HeV and NiV infect cells by a pH-independent membrane fusion mechanism facilitated by their attachment (G) and fusion (F) glycoproteins. Here, several soluble forms of henipavirus F (sF) were engineered and characterized. Recombinant sF was produced by deleting the transmembrane (TM) and cytoplasmic tail (CT) domains and appending a glycosylphosphatidylinositol (GPI) anchor signal sequence followed by GPI-phospholipase D digestion, appending a trimeric coiled-coil (GCNt) domain (sF
GCNt
), or deleting the TM, CT, and fusion peptide domain. These sF glycoproteins were produced as F
0
precursors, and all were apparent stable trimers recognized by NiV-specific antisera. Surprisingly, however, only the GCNt-appended constructs (sF
GCNt
) could elicit cross-reactive henipavirus-neutralizing antibody in mice. In addition, sF
GCNt
constructs could be triggered
in vitro
by protease cleavage and heat to transition from an apparent prefusion to postfusion conformation, transitioning through an intermediate that could be captured by a peptide corresponding to the C-terminal heptad repeat domain of F. The pre- and postfusion structures of sF
GCNt
and non-GCNt-appended sF could be revealed by electron microscopy and were distinguishable by F-specific monoclonal antibodies. These data suggest that only certain sF constructs could serve as potential subunit vaccine immunogens against henipaviruses and also establish important tools for further structural, functional, and diagnostic studies on these important emerging viruses.
Broad-Spectrum Antivirals against 3C or 3C-Like Proteases of Picornaviruses, Noroviruses, and Coronaviruses
Authors: Kim Yunjeong , Lovell Scott , Tiew Kok-Chuan , Mandadapu Sivakoteswara Rao , Alliston Kevin R. , Battaile Kevin P. , Groutas William C. , Chang Kyeong-Ok 
Published: August 2012

ABSTRACT

Phylogenetic analysis has demonstrated that some positive-sense RNA viruses can be classified into the picornavirus-like supercluster, which includes picornaviruses, caliciviruses, and coronaviruses. These viruses possess 3C or 3C-like proteases (3Cpro or 3CLpro, respectively), which contain a typical chymotrypsin-like fold and a catalytic triad (or dyad) with a Cys residue as a nucleophile. The conserved key sites of 3Cpro or 3CLpro may serve as attractive targets for the design of broad-spectrum antivirals for multiple viruses in the supercluster. We previously reported the structure-based design and synthesis of potent protease inhibitors of Norwalk virus (NV), a member of the
Caliciviridae
family. We report herein the broad-spectrum antiviral activities of three compounds possessing a common dipeptidyl residue with different warheads, i.e., an aldehyde (GC373), a bisulfite adduct (GC376), and an α-ketoamide (GC375), against viruses that belong to the supercluster. All compounds were highly effective against the majority of tested viruses, with half-maximal inhibitory concentrations in the high nanomolar or low micromolar range in enzyme- and/or cell-based assays and with high therapeutic indices. We also report the high-resolution X-ray cocrystal structures of NV 3CLpro-, poliovirus 3Cpro-, and transmissible gastroenteritis virus 3CLpro- GC376 inhibitor complexes, which show the compound covalently bound to a nucleophilic Cys residue in the catalytic site of the corresponding protease. We conclude that these compounds have the potential to be developed as antiviral therapeutics aimed at a single virus or multiple viruses in the picornavirus-like supercluster by targeting 3Cpro or 3CLpro.
Internal Catalase Protects Herpes Simplex Virus from Inactivation by Hydrogen Peroxide
Authors: Newcomb William W. , Brown Jay C. 
Published: August 2012

ABSTRACT
Herpes simplex virus 1 (HSV-1) was shown to contain catalase, an enzyme able to detoxify hydrogen peroxide by converting it to water and oxygen. Studies with a catalase inhibitor indicated that virus-associated catalase can have a role in protecting the virus from oxidative inactivation. HSV-1 was found to be more sensitive to killing by hydrogen peroxide in the presence of a catalase inhibitor than in its absence. The results suggest a protective role for catalase during the time HSV-1 spends in the oxidizing environment outside a host cell.
Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins
Authors: Raymond Gregory J. , Race Brent , Hollister Jason R. , Offerdahl Danielle K. , Moore Roger A. , Kodali Ravindra , Raymond Lynne D. , Hughson Andrew G. , Rosenke Rebecca , Long Dan , Dorward David W. , Baron Gerald S. 
Published: August 2012

ABSTRACT

Mammalian prions are thought to consist of misfolded aggregates (protease-resistant isoform of the prion protein [PrP
res
]) of the cellular prion protein (PrP
C
). Transmissible spongiform encephalopathy (TSE) can be induced in animals inoculated with recombinant PrP (rPrP) amyloid fibrils lacking mammalian posttranslational modifications, but this induction is inefficient in hamsters or transgenic mice overexpressing glycosylphosphatidylinositol (GPI)-anchored PrP
C
. Here we show that TSE can be initiated by inoculation of misfolded rPrP into mice that express wild-type (wt) levels of PrP
C
and that synthetic prion strain propagation and selection can be affected by GPI anchoring of the host's PrP
C
. To create prions
de novo
, we fibrillized mouse rPrP in the absence of molecular cofactors, generating fibrils with a PrP
res
-like protease-resistant banding profile. These fibrils induced the formation of PrP
res
deposits in transgenic mice coexpressing wt and GPI-anchorless PrP
C
(wt/GPI
−
) at a combined level comparable to that of PrP
C
expression in wt mice. Secondary passage into mice expressing wt, GPI
−
, or wt plus GPI
−
PrP
C
induced TSE disease with novel clinical, histopathological, and biochemical phenotypes. Contrary to laboratory-adapted mouse scrapie strains, the synthetic prion agents exhibited a preference for conversion of GPI
−
PrP
C
and, in one case, caused disease only in GPI
−
mice. Our data show that novel TSE agents can be generated
de novo
solely from purified mouse rPrP after amplification in mice coexpressing normal levels of wt and anchorless PrP
C
. These observations provide insight into the minimal elements required to create prions
in vitro
and suggest that the PrP
C
GPI anchor can modulate the propagation of synthetic TSE strains.
Porcine Circovirus Type 2 Induces Autophagy via the AMPK/ERK/TSC2/mTOR Signaling Pathway in PK-15 Cells
Authors: Zhu Binglin , Zhou Yingshan , Xu Fei , Shuai Jiangbing , Li Xiaoliang , Fang Weihuan 
Published: August 2012

ABSTRACT
Porcine circovirus type 2 (PCV2) uses autophagy machinery to enhance its replication in PK-15 cells. However, the underlying mechanisms are unknown. By the use of specific inhibitors, RNA interference, and coimmunoprecipitation, we show that PCV2 induces autophagy in PK-15 cells through a pathway involving the kinases AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase 1/2 (ERK1/2), the tumor suppressor protein TSC2, and the mammalian target of rapamycin (mTOR). AMPK and ERK1/2 positively regulate autophagy through negative control of the mTOR pathway by phosphorylating TSC2 in PCV2-infected PK-15 cells. Thus, PCV2 might induce autophagy via the AMPK/ERK/TSC2/mTOR signaling pathway in the host cells, representing a pivotal mechanism for PCV2 pathogenesis.
Comparative Study of Influenza Virus Replication in MDCK Cells and in Primary Cells Derived from Adenoids and Airway Epithelium
Authors: Ilyushina Natalia A. , Ikizler Mine R. , Kawaoka Yoshihiro , Rudenko Larisa G. , Treanor John J. , Subbarao Kanta , Wright Peter F. 
Published: August 2012

ABSTRACT
Although clinical trials with human subjects are essential for determination of safety, infectivity, and immunogenicity, it is desirable to know in advance the infectiousness of potential candidate live attenuated influenza vaccine strains for human use. We compared the replication kinetics of wild-type and live attenuated influenza viruses, including H1N1, H3N2, H9N2, and B strains, in Madin-Darby canine kidney (MDCK) cells, primary epithelial cells derived from human adenoids, and human bronchial epithelium (NHBE cells). Our data showed that despite the fact that all tissue culture models lack a functional adaptive immune system, differentiated cultures of human epithelium exhibited the greatest restriction for all H1N1, H3N2, and B vaccine viruses studied among three cell types tested and the best correlation with their levels of attenuation seen in clinical trials with humans. In contrast, the data obtained with MDCK cells were the least predictive of restricted viral replication of live attenuated vaccine viruses in humans. We were able to detect a statistically significant difference between the replication abilities of the U.S. (A/Ann Arbor/6/60) and Russian (A/Leningrad/134/17/57) cold-adapted vaccine donor strains in NHBE cultures. Since live attenuated pandemic influenza vaccines may potentially express a hemagglutinin and neuraminidase from a non-human influenza virus, we assessed which of the three cell cultures could be used to optimally evaluate the infectivity and cellular tropism of viruses derived from different hosts. Among the three cell types tested, NHBE cultures most adequately reflected the infectivity and cellular tropism of influenza virus strains with different receptor specificities. NHBE cultures could be considered for use as a screening step for evaluating the restricted replication of influenza vaccine candidates.
A Genetic Polymorphism of
FREM1
Is Associated with Resistance against HIV Infection in the Pumwani Sex Worker Cohort
Authors: Luo Ma , Sainsbury James , Tuff Jeffrey , Lacap Philip A. , Yuan Xin-Yong , Hirbod Taha , Kimani Joshua , Wachihi Charles , Ramdahin Sue , Bielawny Thomas , Embree Joanne , Broliden Kristina , Ball T. Blake , Plummer Francis A. 
Published: August 2012

ABSTRACT

A subgroup of women enrolled in the Pumwani sex worker cohort remain seronegative and PCR negative for human immunodeficiency virus type 1 despite repeated exposure through high-risk sex work. Studies have shown that polymorphisms of genes involved in antigen presentation and viral restriction factors are associated with resistance to HIV infection. To discover other possible genetic factors underlying this HIV-resistant phenotype, we conducted an exploratory nonbiased, low-resolution, genome-wide single-nucleotide polymorphism (SNP) analysis comparing 60 HIV-resistant women to 48 HIV-infected controls. The SNP minor allele rs1552896, in an intron of
FREM1
, was significantly associated with the resistant phenotype (
P
= 1.68 × 10
−5
; adjusted
P
= 2.37 × 10
−4
; odds ratio [OR], 9.51; 95% confidence interval [CI], 2.82 to 32.05). We expanded the sample size by genotyping rs1552896 in the Pumwani cohort and comparing 114 HIV-resistant women to 609 HIV-infected controls and confirmed the association (
P
= 1.7 × 10
−4
; OR, 2.67; 95% CI, 1.47 to 4.84). To validate the association in a second cohort, we genotyped 783 women enrolled in a mother-child health study and observed the minor allele of rs1552896 enriched in HIV-uninfected women (
n
= 488) compared to HIV-infected enrollees (
n
= 295) (
P
= 0.036; OR, 1.69; 95% CI, 0.98 to 2.93). Quantitative reverse transcription-PCR showed that
FREM1
mRNA was highly expressed in tissues relevant for HIV-1 infection, and immunohistochemical analysis revealed that FREM1 protein is expressed in the ectocervical mucosa of HIV-resistant women. The significant association of rs1552896 with an HIV-resistant phenotype, together with the expression profile of FREM1 in tissues relevant to HIV infection, suggests that
FREM1
is a potentially novel candidate gene for resistance to HIV infection.
Inclusion Bodies Are a Site of Ebolavirus Replication
Authors: Hoenen Thomas , Shabman Reed S. , Groseth Allison , Herwig Astrid , Weber Michaela , Schudt Gordian , Dolnik Olga , Basler Christopher F. , Becker Stephan , Feldmann Heinz 
Published: August 2012

ABSTRACT
Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for other viruses that produce similar structures have suggested that inclusion bodies might be involved in genome replication and transcription. In order to study filovirus inclusion bodies, we fused mCherry to the ebolavirus polymerase L, which is found in inclusion bodies. The resulting L-mCherry fusion protein was functional in minigenome assays and incorporated into virus-like particles. Importantly, L-mCherry fluorescence in transfected cells was readily detectable and distributed in a punctate pattern characteristic for inclusion bodies. A recombinant ebolavirus encoding L-mCherry instead of L was rescued and showed virtually identical growth kinetics and endpoint titers to those for wild-type virus. Using this virus, we showed that the onset of inclusion body formation corresponds to the onset of viral genome replication, but that viral transcription occurs prior to inclusion body formation. Live-cell imaging further showed that inclusion bodies are highly dynamic structures and that they can undergo dramatic reorganization during cell division. Finally, by labeling nascent RNAs using click technology we showed that inclusion bodies are indeed the site of viral RNA synthesis. Based on these data we conclude that, rather than being inert aggregates of nucleocapsids, ebolavirus inclusion bodies are in fact complex and dynamic structures and an important site at which viral RNA replication takes place.
Complete Genome Sequence of Salmonella Bacteriophage SS3e
Authors: Kim Sung-Hun , Park Jeong-Hyun , Lee Bok-Kwon , Kwon Hyuk-Joon , Shin Ji-Hyun , Kim Jungmin , Kim Shukho 
Published: August 2012

ABSTRACT

A
Salmonella
lytic bacteriophage, SS3e, was isolated, and its genome was sequenced completely. This phage is able to lyse not only various
Salmonella
serovars but also
Escherichia coli
,
Shigella sonnei
,
Enterobacter cloacae
, and
Serratia marcescens
, indicating a broad host specificity. Genomic sequence analysis of SS3e revealed a linear double-stranded DNA sequence of 40,793 bp harboring 58 open reading frames, which is highly similar to
Salmonella
phages SETP13 and MB78.
Complete Genome Sequence of Two Coxsackievirus A1 Strains That Were Cytotoxic to Human Rhabdomyosarcoma Cells
Authors: Sun Qiang , Zhang Yong , Zhu Shuangli , Cui Hui , Tian Huifang , Yan Dongmei , Huang Guohong , Zhu Zhen , Wang Dongyan , Li Xiaolei , Jiang Huafang , An Hongqiu , Xu Wenbo 
Published: August 2012

ABSTRACT

Coxsackievirus A1 (CVA1) belongs to human enterovirus species C within the family
Picornaviridae
, order
Picornavirales
. Two Chinese CVA1 isolates, HT-THLH02F/XJ/CHN/2011 and KS-ZPH01F/XJ/CHN/2011, were isolated from stool specimens of two healthy children in the Xinjiang Uygur autonomous region of China. They were found to elicit cytopathic effects in a human rhabdomyosarcoma cell line, and complete genome sequences of these two CVA1 isolates revealed that natural intertypic recombination events occurred between CVA1 and CVA22.
Biology of a Novel Mycobacteriophage, SWU1, Isolated from Chinese Soil as Revealed by Genomic Characteristics
Authors: Fan Xiangyu , Teng Tieshan , Wang Honghai , Xie Jianping 
Published: August 2012

ABSTRACT

Mycobacteriophage SWU1 is a newly isolated phage from a soil sample collected at Gongping village, Pingchang County, Sichuan Province, China, using
Mycobacterium smegmatis
mc
2
155 as a host. Plaques of SWU1 appear as a unique bull's-eye on an
M. smegmatis
lawn. In this paper, we report the complete genome sequence of SWU1 and some major findings from the analysis result.
Complete Genome of Staphylococcus aureus Phage SA11
Authors: Kim Min Soo , Myung Heejoon 
Published: August 2012

ABSTRACT

A novel lytic bacteriophage, SA11, infecting
Staphylococcus aureus
was isolated, and the whole genome was sequenced. It belongs to the siphoviridae based on electron microscopic observation. It has a linear double-stranded DNA genome of 136,326 bp. Genomic analysis showed that it is distantly related to
Staphylococcus
phages A5W, K, ISP, Sb-1, and G1.
Complete Genome Sequence of Caulobacter crescentus Bacteriophage φCbK
Authors: Panis Gaël , Lambert Christophe , Viollier Patrick H. 
Published: August 2012

ABSTRACT

φCbK is a B3 morphotype bacteriophage of the
Siphoviridae
family that infects
Caulobacter crescentus
, the preeminent model system for bacterial cell cycle studies. The last 4 decades of research with φCbK as a genetic and cytological tool to study the biology of the host warrant an investigation of the phage genome composition. Herein, we report the complete genome sequence of φCbK and highlight unusual features that emerged from its annotation. The complete genome analysis of the φCbK phage provides new insight into its characteristics and potential interactions with its
Caulobacter crescentus
host, setting the stage for future functional studies with φCbK.
Complete Genome Sequence of a Bovine Viral Diarrhea Virus 2 from Commercial Fetal Bovine Serum
Authors: Liu Hua , Li Yan , Gao Mingchun , Wen Kai , Jia Ying , Liu Xiaomei , Zhang Wenlong , Ma Bo , Wang Junwei 
Published: August 2012

ABSTRACT
We isolated a bovine viral diarrhea virus (BVDV) from commercial fetal bovine serum and designated it HLJ-10. The complete genome is 12,284 nucleotides (nt); the open reading frame is 11,694 nt, coding 3,898 amino acids. Phylogenetic analysis indicated that this strain belongs to BVDV group 2.
Complete Genome Sequence of a Novel Porcine Epidemic Diarrhea Virus in South China
Authors: Fan Huiying , Zhang Jie , Ye Yu , Tong Tiezhu , Xie Kangshang , Liao Ming 
Published: August 2012

ABSTRACT
Since early 2010, outbreaks of porcine epidemic diarrhea (PED) have been observed frequently in immunized swine herds in southern China. The suckling piglets are particularly susceptible to porcine epidemic diarrhea virus (PEDV), with a high mortality rate (90%). Recently, a virulent PEDV strain, GD-A, was isolated from an immunized-swine breeding farm in Guangdong, China. This report describes the complete genome sequence of GD-A, and the data will provide important insights into the variation of PEDV field isolates in southern China.
Complete Genome Sequence of an Avian-Origin H3N2 Canine Influenza A Virus Isolated in Farmed Dogs in Southern China
Authors: Su Shuo , Cao Nan , Chen Jidang , Zhao Furong , Li Huatao , Zhao Mingxi , Wang Yanjing , Huang Zhen , Yuan Liguo , Wang Heng , Zhang Guihong , Li Shoujun 
Published: August 2012

ABSTRACT
We report here the complete genomic sequence of an avian-origin H3N2 canine influenza A virus containing multiple mutations in farmed dogs in southern China. Phylogenetic analyses of the sequences of all eight viral RNA segments demonstrated that these are wholly avian influenza viruses of the Asia lineage. To our knowledge, this is the first report of interspecies transmission of an avian H3N2 influenza virus to domestic farm dogs under natural conditions in Southern China. The amino acid information provided herein suggests that continued study is required to determine if this virus could be established in the farm dog population and pose potential threats to public health.
Complete Genome Sequence of Ikoma Lyssavirus
Authors: Marston Denise A. , Ellis Richard J. , Horton Daniel L. , Kuzmin Ivan V. , Wise Emma L. , McElhinney Lorraine M. , Banyard Ashley C. , Ngeleja Chanasa , Keyyu Julius , Cleaveland Sarah , Lembo Tiziana , Rupprecht Charles E. , Fooks Anthony R. 
Published: August 2012

ABSTRACT

Lyssaviruses (family
Rhabdoviridae
) constitute one of the most important groups of viral zoonoses globally. All lyssaviruses cause the disease rabies, an acute progressive encephalitis for which, once symptoms occur, there is no effective cure. Currently available vaccines are highly protective against the predominantly circulating lyssavirus species. Using next-generation sequencing technologies, we have obtained the whole-genome sequence for a novel lyssavirus, Ikoma lyssavirus (IKOV), isolated from an African civet in Tanzania displaying clinical signs of rabies. Genetically, this virus is the most divergent within the genus
Lyssavirus
. Characterization of the genome will help to improve our understanding of lyssavirus diversity and enable investigation into vaccine-induced immunity and protection.
Genome Sequence of a Bombyx mori Nucleopolyhedrovirus Strain with Cubic Occlusion Bodies
Authors: Cheng Ruo-Lin , Xu Yi-Peng , Zhang Chuan-Xi 
Published: August 2012

ABSTRACT

Bombyx mori
nucleopolyhedrovirus (BmNPV) is a typical species of
Baculoviridae
. The complete genome sequence of a BmNPV strain with cubic occlusion bodies is reported here. The genome of this strain consists of 127,465 nucleotides with a G+C content of 40.36% and is 97.3% and 97.5% identical to those of BmNPV strain T3 and
Bombyx mandarina
NPV S1, respectively. Despite the abnormal polyhedra it forms, the
polyhedrin
gene of the BmNPV cubic strain is 100% identical to those of the other two strains. Baculovirus repeated ORFs and homologous repeat regions cause the major differences in genome size of these BmNPV isolates.