Abstract:
UNLABELLED:Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that the HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable than the HAs from other seasonal influenza virus strains. Here we show that residue 205 in HA1 and residue 399 in the B loop of HA2 (residue 72, HA2 numbering) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at a higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity. IMPORTANCE:Influenza virus hemagglutinin (HA) is the principal antigen in inactivated influenza vaccines and the target of protective antibodies. However, the influenza A virus HA is highly variable, necessitating frequent vaccine changes to match circulating strains. Sequence changes in HA affect not only antigenicity but also HA stability, which has important implications for vaccine production, as well as viral adaptation to hosts. HA from the pandemic 2009 H1N1 influenza A virus is less stable than other recent seasonal influenza virus HAs, but the molecular interactions that contribute to HA stability are not fully understood. Here we identify molecular interactions between specific residues in the surface and transmembrane subunits of HA that help regulate the HA conformational changes needed for HA stability and virus entry. These findings contribute to our understanding of the molecular mechanisms controlling HA function and antigen stability.
journal_name
J Viroljournal_title
Journal of virologyauthors
Wang W,DeFeo CJ,Alvarado-Facundo E,Vassell R,Weiss CDdoi
10.1128/JVI.00939-15subject
Has Abstractpub_date
2015-10-01 00:00:00pages
10602-11issue
20eissn
0022-538Xissn
1098-5514pii
JVI.00939-15journal_volume
89pub_type
杂志文章abstract::The human papillomavirus type 11 (HPV-11) L1 major capsid protein can be trypsinized to generate recombinant capsomeres that retain HPV genotype-restricted capsid antigenicity (M. Li, T. P. Cripe, P. A. Estes, M. K. Lyon, R. C. Rose, and R. L. Garcea, J. Virol. 71:2988-2995, 1997). In the present study, HPV-11 virion-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.7.6151-6154.1998
更新日期:1998-07-01 00:00:00
abstract::We have used a V3-specific heteroduplex tracking assay (V3-HTA) with probes from two different human immunodeficiency virus type 1 (HIV-1) subtypes to examine the extent and pace of HIV-1 evolution late in infection. Twenty-four subjects with advanced HIV-1 infection (CD4(+) T-cell count, <100/microl) and stable viral...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.18.8494-8501.2000
更新日期:2000-09-01 00:00:00
abstract:UNLABELLED:Macrophages must react to a large number of pathogens and their effects. In chronic HIV infection, the microenvironment changes with an influx of microbial products that trigger Toll-like receptors (TLRs). That dynamic nature can be replicated ex vivo by the proinflammatory (M1-polarized) and alternatively a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01053-14
更新日期:2014-09-01 00:00:00
abstract:UNLABELLED:Marek's disease virus (MDV), an alphaherpesvirus, is the causative agent of a lethal disease in chickens characterized by generalized nerve inflammation and rapid lymphoma development. The extensive colinearity of the MDV genome with those of related herpesviruses has eased functional characterization of man...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02687-14
更新日期:2015-01-15 00:00:00
abstract::The bacteriophage T4 unf gene, known to be involved in the arrest of transcription from cytosine-containing DNA, is unessential except in Escherichia coli strains containing plasmid pR386. Comparative genetic and biochemical analyses of parameters of unf+ and unf- phage growth in host cells isogenic except for the pre...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.2.430-439.1985
更新日期:1985-02-01 00:00:00
abstract::Thirteen point mutations targeting predicted domains conserved in homologous protein kinases were introduced into the UL97 coding region of the human cytomegalovirus. All mutagenized proteins were expressed in cells infected with recombinant vaccinia viruses (rVV). Several mutations drastically reduced ganciclovir (GC...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.10.8898-8901.1999
更新日期:1999-10-01 00:00:00
abstract::ETnII elements are mobile members of the repetitive early transposon family of mouse long terminal repeat (LTR) retroelements and have caused a number of mutations by inserting into genes. ETnII sequences lack retroviral genes, but the recent discovery of related MusD retroviral elements with regions similar to gag, p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.21.11448-11458.2003
更新日期:2003-11-01 00:00:00
abstract::The mammalian APOBEC3 family of cytidine deaminases includes members that can act as potent inhibitors of retroviral infectivity and retrotransposon mobility. Here, we have examined whether the alpharetrovirus Rous sarcoma virus (RSV) is susceptible to inhibition by a range of human APOBEC3 proteins. We report that RS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01646-07
更新日期:2007-12-01 00:00:00
abstract::The RNA produced in vivo from bacteriophage phiX174 DNA has been analyzed by polyacrylamide-agarose gel electrophoresis and sedimentation in dimethyl sulfoxide gradients, and the results of Hayashi and Hayashi (1970) have been confirmed and extended. An efficient procedure for recovery of RNA from gels, followed by a ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.1.151-160.1975
更新日期:1975-01-01 00:00:00
abstract::Influenza A viruses of the H9N2 subtype are endemic in poultry in many Eurasian countries and have occasionally caused clinical respiratory diseases in humans. While some avian H9N2 viruses have glutamine (Q) at amino acid position 226 of the hemagglutinin (HA) receptor-binding site, an increasing number of isolates h...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02827-06
更新日期:2007-05-01 00:00:00
abstract::The integrase protein of human immunodeficiency virus type 1 removes two nucleotides from the 3' ends of reverse-transcribed human immunodeficiency virus type 1 DNA (3' processing) and covalently inserts the processed ends into a target DNA (DNA strand transfer). Mutant integrase proteins that lack the amino-and/or ca...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.5911-5917.1994
更新日期:1994-09-01 00:00:00
abstract::Recent studies have demonstrated that influenza A virus infection activates the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway by binding of influenza NS1 protein to the p85 regulatory subunit of PI3K. Our previous study proposed that two polyproline motifs in NS1 (amino acids 164 to 167 [PXXP], SH3 bindin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01427-07
更新日期:2007-12-01 00:00:00
abstract::Egress of wrapped virus (WV) to the cell periphery following vaccinia virus (VACV) replication is dependent on interactions with the microtubule motor complex kinesin-1 and is mediated by the viral envelope protein A36. Here we report that ectromelia virus (ECTV), a related orthopoxvirus and the causative agent of mou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06636-11
更新日期:2012-07-01 00:00:00
abstract::We used deep sequencing of poly(A) RNA to characterize the transcriptome of an economically important eel virus, anguillid herpesvirus 1 (AngHV1), at a stage during the lytic life cycle when infectious virus was being produced. In contrast to the transcription of mammalian herpesviruses, the overall level of antisense...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01271-12
更新日期:2012-09-01 00:00:00
abstract::TMC125 is a potent new investigational nonnucleoside reverse transcriptase inhibitor (NNRTI) that is active against human immunodeficiency virus type 1 (HIV-1) with resistance to currently licensed NNRTIs. Sequential passage experiments with both wild-type virus and NNRTI-resistant virus were performed to identify mut...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.20.12773-12782.2005
更新日期:2005-10-01 00:00:00
abstract::The TAATGARAT motif in the herpes simplex virus (HSV) immediate-early (IE) gene promoters plays a key role in their activation by the Oct-1-Vmw65 complex, but its role in mediating inhibitory effects of cellular octamer-binding proteins is less clear. We have used indicator viruses containing reporter constructs with ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.4.3495-3500.1998
更新日期:1998-04-01 00:00:00
abstract::The human T-cell leukemia virus type 1 (HTLV-1) transmembrane glycoprotein has a 24-amino-acid cytoplasmic domain whose function in the viral life cycle is poorly understood. We introduced premature-stop mutations and 18 single-amino-acid substitutions into this domain and studied their effects on cell-to-cell transmi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9659-9663.1999
更新日期:1999-11-01 00:00:00
abstract::A lysate from hypotonically swollen polyoma-infected BALB/3T3 cells incorporated labeled deoxynucleotide triphosphates into both viral and cellular DNAs. The incorporation was stimulated by the presence of ATP, deoxynucleotide triphosphates, thiols, and magnesium ions. Strong inhibition of incorporation was observed w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.1.125-139.1974
更新日期:1974-01-01 00:00:00
abstract::Marek's disease virus (MDV) is a herpesvirus of chickens that induces T lymphomas and tumors within 4 to 5 weeks of infection. Although the ability of MDV to induce tumors was demonstrated many years ago and although a number of viral oncogenic proteins have been identified, the mechanism by which the MDV is implicate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.10.5985-5996.2003
更新日期:2003-05-01 00:00:00
abstract::MicroRNAs (miRNAs) are potent RNA regulators of gene expression. Some viruses encode miRNAs, most of unknown function. The majority of viral miRNAs are not conserved, and whether any have conserved functions remains unclear. Here, we report that two human polyomaviruses associated with serious disease in immunocomprom...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01144-08
更新日期:2008-10-01 00:00:00
abstract::The ATP-dependent DNase activity of Escherichia coli disappeared or was markedly reduced after infection with double-stranded DNA phages, T2, T3, T4, T5, T6, T7, lambda, phi80, and P1, but not with the single-stranded DNA phage f1, or the RNA phage Qbeta. This DNase activity was not reduced when chloramphenicol was ad...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.6.1611-1612.1974
更新日期:1974-12-01 00:00:00
abstract::Viral recombination has been postulated to play two roles in the development of human immunodeficiency virus (HIV) resistance to antiretroviral drugs. First, recombination has the capacity to associate resistance mutations expressed by distinct viruses, thereby contributing to the development of viruses with improved ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00083-07
更新日期:2007-07-01 00:00:00
abstract::The human cyclin T1 (hCycT1) protein from the positive transcription elongation factor b (P-TEFb) binds the transactivator Tat and the transactivation response (TAR) RNA stem loop from human immunodeficiency virus type 1 (HIV). This complex activates the elongation of viral transcription. To create effective inhibitor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.21.10873-10881.2002
更新日期:2002-11-01 00:00:00
abstract::The ability of human immunodeficiency virus type 1 (HIV-1) to transduce nondividing cells is key to infecting terminally differentiated macrophages, which can serve as a long-term reservoir of HIV-1 infection. The mutation N57A in the viral CA protein renders HIV-1 cell cycle dependent, allowing examination of HIV-1 i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00214-19
更新日期:2019-04-17 00:00:00
abstract::Despite intensive research on the identification of T-cell epitopes in cattle after foot-and-mouth disease virus (FMDV) infection during the last 20 years, knowledge of major histocompatibility complex (MHC) restriction and anchor residues of such epitopes is still sparse. Therefore, as a first step, we tested lymphoc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01534-08
更新日期:2009-05-01 00:00:00
abstract::Transient transfection assays indicated that A2L is one of three vaccinia virus intermediate genes that are required for the transcriptional transactivation of viral late genes. We have expressed the A2L open reading frame in Escherichia coli and shown by blotting experiments that the 26-kDa protein binds zinc, a prop...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.5749-5753.1993
更新日期:1993-10-01 00:00:00
abstract::Severe acute respiratory syndrome (SARS), caused by a novel coronavirus (CoV) known as SARS-CoV, is a contagious and life-threatening respiratory illness with pneumocytes as its main target. A full understanding of how SARS-CoV would interact with lung epithelial cells will be vital for advancing our knowledge of SARS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.15.9470-9479.2005
更新日期:2005-08-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) exhibits a high level of genetic variation generated by frequent mutation and genetic recombination during reverse transcription. We have measured HIV-1 recombination rates in T cells in one round of virus replication. It was recently proposed that HIV-1 recombines far more ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.14.9337-9340.2005
更新日期:2005-07-01 00:00:00
abstract::The RNA elements that are required for replication of defective interfering (DI) RNA of the JHM strain of mouse hepatitis virus (MHV) consist of three discontinuous genomic regions: about 0.46 to 0.47 kb from both terminal sequences and an internal 58-nucleotide (nt)-long sequence (58-nt region) present at about 0.9 k...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.10.7926-7933.1998
更新日期:1998-10-01 00:00:00
abstract::Using a method for freeze-drying intact cells, uninfected and murine leukemia virus (MuLV)-infected JLSV9 cell surfaces, as well as murine mammary tumor virus (MuMTV)-infected cell surfaces, were examined by electron microscopy. The 10-nm knobs of MuLV and the 5-nm spikes of MuMTV were clearly revealed on the surfaces...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.1.358-365.1977
更新日期:1977-01-01 00:00:00