Abstract:
UNLABELLED:Phosphoinositides and phosphoinositide binding proteins play a critical role in membrane and protein trafficking in eukaryotes. Their critical role in replication of cytoplasmic viruses has just begun to be understood. Poxviruses, a family of large cytoplasmic DNA viruses, rely on the intracellular membranes to develop their envelope, and poxvirus morphogenesis requires enzymes from the cellular phosphoinositide metabolic pathway. However, the role of phosphoinositides in poxvirus replication remains unclear, and no poxvirus proteins show any homology to eukaryotic phosphoinositide binding domains. Recently, a group of poxvirus proteins, termed viral membrane assembly proteins (VMAPs), were identified as essential for poxvirus membrane biogenesis. A key component of VMAPs is the H7 protein. Here we report the crystal structure of the H7 protein from vaccinia virus. The H7 structure displays a novel fold comprised of seven α-helices and a highly curved three-stranded antiparallel β-sheet. We identified a phosphoinositide binding site in H7, comprised of basic residues on a surface patch and the flexible C-terminal tail. These residues were found to be essential for viral replication and for binding of H7 to phosphatidylinositol-3-phosphate (PI3P) and phosphatidylinositol-4-phosphate (PI4P). Our studies suggest that phosphoinositide binding by H7 plays an essential role in poxvirus membrane biogenesis. IMPORTANCE:Poxvirus viral membrane assembly proteins (VMAPs) were recently shown to be essential for poxvirus membrane biogenesis. One of the key components of VMAPs is the H7 protein. However, no known structural motifs could be identified from its sequence, and there are no homologs of H7 outside the poxvirus family to suggest a biochemical function. We have determined the crystal structure of the vaccinia virus (VACV) H7 protein. The structure displays a novel fold with a distinct and positively charged surface. Our data demonstrate that H7 binds phosphatidylinositol-3-phosphate and phosphatidylinositol-4-phosphate and that the basic surface patch is indeed required for phosphoinositide binding. In addition, mutation of positively charged residues required for lipid binding disrupted VACV replication. Phosphoinositides and phosphoinositide binding proteins play critical roles in membrane and protein trafficking in eukaryotes. Our study demonstrates that VACV H7 displays a novel fold for phosphoinositide binding, which is essential for poxvirus replication.
journal_name
J Viroljournal_title
Journal of virologyauthors
Kolli S,Meng X,Wu X,Shengjuler D,Cameron CE,Xiang Y,Deng Jdoi
10.1128/JVI.03073-14subject
Has Abstractpub_date
2015-02-01 00:00:00pages
2209-19issue
4eissn
0022-538Xissn
1098-5514pii
JVI.03073-14journal_volume
89pub_type
杂志文章abstract::UR2 is a newly characterized avian sarcoma virus whose genome contains a unique sequence that is not related to the sequences of other avian sarcoma virus transforming genes thus far identified. This unique sequence, termed ros, is fused to part of the viral gag gene. The product of the fused gag-ros gene of UR2 is a ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.42.1.228-236.1982
更新日期:1982-04-01 00:00:00
abstract::The herpes simplex virus genome consists of two components, L and S, that invert relative to each other to yield four isomeric arrangements, prototype (P), inversion of the S component (Is), inversion of the L component (Il), and inversion of both components (Isl). Previous studies have shown that the 500-base-pair a ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.2.583-591.1986
更新日期:1986-05-01 00:00:00
abstract::H5N1 highly pathogenic avian influenza virus (HPAIV) has continued to spread and poses a significant threat to both animal and human health. Current influenza vaccine strategies have limitations that prevent their effective use for widespread inoculation of animals in the field. Vaccine strains of Newcastle disease vi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01514-06
更新日期:2007-01-01 00:00:00
abstract::The retroviral primary transcription product is a multifunctional RNA that is utilized as pre-mRNA, mRNA, and genomic RNA. The relationship between human immunodeficiency virus type 1 (HIV-1) unspliced transcripts used as mRNA for viral protein synthesis and as virion precursor RNA (vpRNA) for encapsidation remains an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.24.11531-11537.2000
更新日期:2000-12-01 00:00:00
abstract::The herpes simplex virus type 1 (HSV-1) alpha protein ICP27 regulates the transition between the delayed-early and late phases of the viral infection. Previous genetic analyses have suggested that the important functional domains of ICP27 map to its carboxyl-terminal half. One striking feature of the primary sequence ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.4.1778-1787.1993
更新日期:1993-04-01 00:00:00
abstract::Human T-cell leukemia virus (HTLV) Tax protein has been implicated in the HTLV oncogenic process, primarily due to its pleiotropic effects on cellular genes involved in growth regulation and cell cycle control. To date, several approaches attempting to correlate Tax activation of the CREB/activating transcription fact...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.6.2655-2662.2000
更新日期:2000-03-01 00:00:00
abstract::A promoter-trap retrovirus has been constructed in which a promoterless polyomavirus middle T antigen gene was inserted in the U3 region of the long terminal repeat of a replication-competent Moloney murine leukemia virus. The resulting virus, designated PyT, was used to infect mouse mammary glands in situ. As expecte...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.10.6810-6815.1996
更新日期:1996-10-01 00:00:00
abstract::We present an antiviral-immunomodulatory therapeutic strategy involving the chemokine receptor antagonist Met-RANTES, which yields significant survival in the setting of an otherwise fatal respiratory virus infection. In previous work, we demonstrated that infection with the natural rodent pathogen pneumonia virus of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.15.7984-7989.2004
更新日期:2004-08-01 00:00:00
abstract::Virus-specific proteins were examined in cultured cells infected with bovine viral diarrhea virus. By using antisera obtained from virus-infected animals, three major virus-specific polypeptides with molecular weights of 115,000 (115K), 80K, and 55K were observed. Minor proteins of 45,000 and 38,000 daltons were also ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.2.666-669.1984
更新日期:1984-05-01 00:00:00
abstract::Feline herpesvirus produces characteristic morphological alterations in feline kidney cells. Nucleocapsid particles are formed in infected nuclei and are enveloped as they pass through the modified inner nuclear membrane. Aggregates of dense granular material and filamentous structures also regularly appear in infecte...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.5.5.617-623.1970
更新日期:1970-05-01 00:00:00
abstract::Under the immune pressure of cytotoxic T cells (CTLs), hepatitis B virus (HBV) evolves to accumulate mutations more likely within epitopes to evade immune detection. However, little is known about the specific patterns of the immune pressure-associated HBV mutation of T-cell epitopes and their link to disease progress...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02120-17
更新日期:2018-08-16 00:00:00
abstract::H5N1 and H9N2 avian influenza virus subtypes top the World Health Organization's list for the greatest pandemic potential. Inactivated H5N1 vaccines induce limited immune responses and, in the case of live-attenuated influenza virus vaccines (LAIV), there are safety concerns regarding the possibility of reassortment b...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02490-12
更新日期:2013-05-01 00:00:00
abstract:UNLABELLED:The positive-sense RNA genome of Sweet potato feathery mottle virus (SPFMV) (genus Potyvirus, family Potyviridae) contains a large open reading frame (ORF) of 3,494 codons translatable as a polyprotein and two embedded shorter ORFs in the -1 frame: PISPO, of 230 codons, and PIPO, of 66 codons, located in the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02360-15
更新日期:2016-01-20 00:00:00
abstract::The emergence in 1997 and continuance today of a highly lethal H5N1 avian influenza virus (AIV) causing human disease has raised concern about an impending pandemic and the need for a vaccine to prepare for such an occurrence. We previously generated an efficacious vesicular stomatitis virus (VSV)-based AIV vaccine ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02637-09
更新日期:2010-05-01 00:00:00
abstract::A more complete assessment of ovine prion strain diversity will be achieved by complementing biological strain typing in conventional and ovine PrP transgenic mice with a biochemical analysis of the resultant PrPSc. This will provide a correlation between ovine prion strain phenotype and the molecular nature of differ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01454-08
更新日期:2008-11-01 00:00:00
abstract:UNLABELLED:Recent evidence suggests that even in treated infections, human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication may continue in lymph nodes (LN), serving as a potential virus reservoir. Here we investigated the effects of lentivirus infection on natural killer (NK) cell frequ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00660-15
更新日期:2015-07-01 00:00:00
abstract::The infection of human fetal thymus organ cultures (FTOC) with coxsackievirus B4 E2 (CVB4 E2) was investigated. Both positive- and negative-strand viral RNA were detected by real-time quantitative reverse transcription-PCR (RT-PCR) in CVB4 E2-infected FTOC, which supported high yields of virus production (approximatel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.18.9854-9861.2004
更新日期:2004-09-01 00:00:00
abstract::The lymphocytic choriomeningitis virus (LCMV) genome consists of a large RNA segment and a small RNA segment. The three major structural proteins of this virus are an internal nucleoprotein and two surface glycoproteins. Intertypic reassortants between the Armstrong and WE strains of LCMV were made to map proteins enc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.3.966-968.1985
更新日期:1985-03-01 00:00:00
abstract::The expression of a human immunodeficiency virus (HIV) type 1 provirus (F12-HIV) cloned from a nonproducer, chronically infected CD4 down-regulated Hut-78 cell clone (F12) does not lead to the formation of viral particles and, upon transfection in HeLa CD4+ cells, confers resistance to HIV superinfection without affec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.6618-6626.1995
更新日期:1995-11-01 00:00:00
abstract::Merkel cell polyomavirus (MCPyV) is the major cause for Merkel cell carcinoma (MCC), a rare but highly aggressive skin cancer predominantly found in elderly and immunosuppressed patients. The early viral gene products large T-antigen (LT) and small T-antigen (sT) are important for efficient viral DNA replication, and ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01638-19
更新日期:2020-02-14 00:00:00
abstract::Individuals infected with the human immunodeficiency virus (HIV) experience a marked loss of CD4+ T lymphocytes, leading to fatal immunodeficiency. The mechanisms causing the depletion of these cells are not yet understood. In this study, we observed that CD4+ T lymphocytes from HIV type 1 (HIV-1)-infected and uninfec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.6925-6931.1995
更新日期:1995-11-01 00:00:00
abstract:UNLABELLED:Pattern recognition receptors (PRR) sense certain molecular patterns uniquely expressed by pathogens. Retinoic-acid-inducible gene I (RIG-I) is a cytosolic PRR that senses viral nucleic acids and induces innate immune activation and secretion of type I interferons (IFNs). Here, using influenza vaccine antige...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02273-14
更新日期:2014-12-01 00:00:00
abstract::In infected cells, hepatitis C virus (HCV) induces the formation of membrane alterations referred to as membranous webs, which are sites of RNA replication. In addition, HCV RNA replication also occurs in smaller membrane structures that are associated with the endoplasmic reticulum. However, cellular mechanisms invol...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01190-09
更新日期:2010-01-01 00:00:00
abstract::Utilizing a human cytomegalovirus-specific fusion inhibitor and an antiglycoprotein H antibody, we studied the role of virion fusion in interferon-stimulated gene (ISG) induction. Our results indicate that ISG induction does not occur when virion-mediated, post-high-affinity attachment events are inhibited by either r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.12.6688-6691.2004
更新日期:2004-06-01 00:00:00
abstract::Mosquito-borne alphaviruses, which replicate alternately and obligately in mosquitoes and vertebrates, appear to experience lower rates of evolution than do many RNA viruses that replicate solely in vertebrates. This genetic stability is hypothesized to result from the alternating host cycle, which constrains evolutio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.22.14253-14260.2005
更新日期:2005-11-01 00:00:00
abstract::Cottontail rabbit papillomavirus induces strictly epithelial tumors in both cottontail and domestic rabbits. A high proportion of the initial benign papillomas progress within 8 to 14 months to invasive carcinomas. With the help of mRNA-specific riboprobes for E6, E7, E1, E2, L1 and L2, we investigated by in situ hybr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.6.3620-3630.1994
更新日期:1994-06-01 00:00:00
abstract::The family Geminiviridae comprises seven genera differentiated by genome organization, sequence similarity, and insect vector. Capulavirus, an eighth genus, has been proposed to accommodate two newly discovered highly divergent geminiviruses that presently have no known vector. Alfalfa leaf curl virus, identified here...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.00453-15
更新日期:2015-09-01 00:00:00
abstract::Replication of human papillomavirus type 11 (HPV-11) DNA requires the full-length viral E1 and E2 proteins (C.-M. Chiang, M. Ustav, A. Stenlund, T. F. Ho, T. R. Broker, and L. T. Chow, Proc. Natl. Acad. Sci. USA 89:5799-5803, 1992). Using transient transfection of subgenomic HPV DNA into hamster CHO and human 293 cell...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.9.5224-5231.1992
更新日期:1992-09-01 00:00:00
abstract::The development of cancer vaccines requires approaches to induce expansion and functional differentiation of tumor antigen-specific cytotoxic T lymphocyte (CTL) effectors which posses cytolytic capability and produce cytokines. Efficient induction of such cells is hindered by the poor immunogenicity of tumor antigens ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.13.7411-7424.2003
更新日期:2003-07-01 00:00:00
abstract::The C-type lectins DC-SIGN and DC-SIGNR [collectively referred to as DC-SIGN(R)] bind and transmit human immunodeficiency virus (HIV) and simian immunodeficiency virus to T cells via the viral envelope glycoprotein (Env). Other viruses containing heavily glycosylated glycoproteins (GPs) fail to interact with DC-SIGN(R...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.2.1337-1346.2003
更新日期:2003-01-01 00:00:00