Abstract:
:Cholesterol has been implicated in various viral life cycle steps for different enveloped viruses, including viral entry into host cells, cell-cell fusion, and viral budding from infected cells. Enveloped viruses acquire their membranes from their host cells. Though cholesterol has been associated with binding and entry of various enveloped viruses into cells, cholesterol's exact function in the viral-cell membrane fusion process remains largely elusive, particularly for the paramyxoviruses. Further, paramyxoviral fusion occurs at the host cell membrane and is essential for both virus entry (virus-cell fusion) and syncytia formation (cell-cell fusion), central to viral pathogenicity. Nipah virus (NiV) is a deadly member of the Paramyxoviridae family, which also includes Hendra, measles, mumps, human parainfluenza, and various veterinary viruses. The zoonotic NiV causes severe encephalitis, vasculopathy, and respiratory symptoms, leading to a high mortality rate in humans. We used NiV as a model to study the role of membrane cholesterol in paramyxoviral membrane fusion. We used a combination of methyl-beta cyclodextrin (MβCD), lovastatin, and cholesterol to deplete or enrich cell membrane cholesterol outside cytotoxic concentrations. We found that the levels of cellular membrane cholesterol directly correlated with the levels of cell-cell fusion induced. These phenotypes were paralleled using NiV/vesicular stomatitis virus (NiV/VSV) pseudotyped viral infection assays. Remarkably, our mechanistic studies revealed that cholesterol reduces an early F-triggering step but enhances a late fusion pore formation step in the NiV membrane fusion cascade. Thus, our results expand our mechanistic understanding of the paramyxoviral/henipaviral entry and cell-cell fusion processes.IMPORTANCE Cholesterol has been implicated in various steps of the viral life cycle for different enveloped viruses. Nipah virus (NiV) is a highly pathogenic enveloped virus in the Henipavirus genus within the Paramyxoviridae family, capable of causing a high mortality rate in humans and high morbidity in domestic and agriculturally important animals. The role of cholesterol for NiV or the henipaviruses is unknown. Here we show that the levels of cholesterol influence the levels of NiV-induced cell-cell membrane fusion during syncytia formation, and virus-cell membrane fusion during viral entry. Further, the specific role of cholesterol in membrane fusion is not well defined for the paramyxoviruses. We show that the levels of cholesterol affect an early F-triggering step and a late fusion pore formation step during the membrane fusion cascade. Thus, our results expand our mechanistic understanding of the viral entry and cell-cell fusion processes, which may aid the development of antivirals.
journal_name
J Viroljournal_title
Journal of virologyauthors
Contreras EM,Johnston GP,Buchholz DW,Ortega V,Monreal IA,Zamora JLR,Cheung T,Aguilar HCdoi
10.1128/JVI.02323-20subject
Has Abstractpub_date
2021-01-06 00:00:00eissn
0022-538Xissn
1098-5514pii
JVI.02323-20pub_type
杂志文章abstract::Herpesviruses use a cascade of interactions with different cell surface molecules to gain entry into cells. In many cases, this involves binding to abundant glycosaminoglycans or integrins followed by interactions with more limited cell surface proteins, leading to fusion with cellular membranes. Human cytomegalovirus...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01623-08
更新日期:2008-12-01 00:00:00
abstract::Gene transfer to differentiated airway epithelia with existing viral vectors is very inefficient when they are applied to the apical surface. This largely reflects the polarized distribution of receptors on the basolateral surface. To identify new receptor-ligand interactions that might be used to redirect vectors to ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.19.9234-9239.2000
更新日期:2000-10-01 00:00:00
abstract::The HXLF (HindIII-X left reading frame) gene family is a group of five genes that share one or two regions of homology and are arranged in tandem within the short unique component of the human cytomegalovirus genome (K. Weston and B.G. Barrell, J. Mol. Biol. 192:177-208, 1986). These genes were cloned into an SP6 expr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.6.1956-1962.1988
更新日期:1988-06-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) strains can be separated into genetic subtypes based on phylogenetic analysis of the envelope gene. Once it had been shown that population-wide intrasubtype genetic variation of HIV-1 strains increases in the course of the AIDS epidemic, it remained uncertain whether HIV-1 s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.9.6332-6338.1997
更新日期:1997-09-01 00:00:00
abstract::The VP24 protein plays an essential, albeit poorly understood role in the filovirus life cycle. VP24 is only 30% identical between Marburg virus and the ebolaviruses. Furthermore, VP24 from the ebolaviruses is immunosuppressive, while that of Marburg virus is not. The crystal structure of Marburg virus VP24, presented...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03565-13
更新日期:2014-05-01 00:00:00
abstract::The characteristics of fusion of respiratory syncytial virus (RSV) with HEp-2 cells were studied by the R18 fluorescence dequenching assay of membrane fusion. A gradual increase in fluorescence intensity indicative of virion-cell fusion was observed when R18-labeled RSV was incubated with HEp-2 cells. Approximately 35...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.8.4063-4069.1991
更新日期:1991-08-01 00:00:00
abstract::Although highly active antiretroviral therapy (HAART) for human immunodeficiency virus type 1 (HIV-1) infection can reduce levels of HIV-1 RNA in plasma to below the limit of detection, replication-competent forms of the virus persist in all infected individuals. One form of persistence involves a stable reservoir of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.18.9481-9492.2002
更新日期:2002-09-01 00:00:00
abstract:UNLABELLED:Of the various genetic subtypes of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV), only in subtype C of HIV-1 is a genetically variant NF-κB binding site found at the core of the viral promoter in association with a subtype-specific Sp1III motif. How the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00308-16
更新日期:2016-07-27 00:00:00
abstract::Influenza causes significant morbidity in tropical regions; however, unlike in temperate zones, influenza in the tropics is not strongly associated with a given season. We have recently shown that influenza virus transmission in the guinea pig model is most efficient under cold, dry conditions, which are rare in the t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00325-08
更新日期:2008-06-01 00:00:00
abstract::During the course of experiments designed to isolate deletion mutants of herpes simplex virus type 1 in the gene encoding the major DNA-binding protein, ICP8, a mutant, d61, that grew efficiently in ICP8-expressing Vero cells but not in normal Vero cells was isolated (P. K. Orberg and P. A. Schaffer, J. Virol. 61:1136...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.11.3528-3535.1987
更新日期:1987-11-01 00:00:00
abstract::Hepatitis C virus (HCV) remains a significant threat to the general health of the world's population, and there is a pressing need for the development of new treatments and preventative vaccines. Here, we describe the generation of retrovirus-based pseudoparticles (HCVpp) incorporating a panel of full-length E1E2 clon...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.17.11095-11104.2005
更新日期:2005-09-01 00:00:00
abstract::Molecular clones of closed circular DNA molecules of a mink cell focus-inducing murine leukemia virus (MCF-13 MuLV) were generated. Closed circular DNA molecules isolated from a Hirt extraction of recently infected NIH/3T3 cells were inserted at their unique EcoRI site into lambda gtWES.lambda B. Restriction endonucle...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.1.348-351.1982
更新日期:1982-07-01 00:00:00
abstract::Envelope glycoprotein E(rns) of classical swine fever virus (CSFV) has been shown to contain RNase activity and is involved in virus infection. Two short regions of amino acids in the sequence of E(rns) are responsible for RNase activity. In both regions, histidine residues appear to be essential for catalysis. They w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.1.151-157.1998
更新日期:1998-01-01 00:00:00
abstract::Heterozygous replicative form molecules of bacteriophage phiX174 deoxyribonucleic acid (DNA) have been constructed in vitro. These are composed of viral strands extracted from purified preparations of phage bearing ts mutations and complementary strands of either half length or full length synthesized with purified DN...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.5.603-611.1971
更新日期:1971-05-01 00:00:00
abstract::Mlvi-1 defines a locus of proviral integration in rat thymomas induced by Moloney murine leukemia virus. pvt-1/Mis-1 represents an independently identified locus which becomes rearranged either by chromosomal translocation in murine plasmacytomas or by provirus insertion in retrovirus-induced murine and rat thymic lym...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.2366-2369.1989
更新日期:1989-05-01 00:00:00
abstract::Rfv3 is an autosomal dominant gene that influences the recovery of resistant mice from Friend retrovirus (FV) infection by limiting viremia and promoting a more potent neutralizing antibody response. We previously reported that Rfv3 is encoded by Apobec3, an innate retrovirus restriction factor. However, it was recent...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01838-10
更新日期:2011-01-01 00:00:00
abstract::The relative contribution of measles virus hemagglutinin (H)- or fusion protein (F)-specific antibodies to virus neutralization (VN) has not been demonstrated. We have depleted these specific antibodies from sera collected from young adults, who had been vaccinated during childhood, by prolonged incubation with viable...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.17.11547-11551.2005
更新日期:2005-09-01 00:00:00
abstract::NF-D is a ubiquitous nuclear factor that has been shown to bind specifically to a DNA element in the polyomavirus regulatory region. In this report, we demonstrate that NF-D is either identical or very similar to a transcription factor that has been variously named YY1, delta, NF-E1, UCRBP, or CF1. Moreover, we show t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.1433-1438.1996
更新日期:1996-03-01 00:00:00
abstract::Early sensing of viral components or infection-induced tissue damage is a prerequisite for the successful control of pathogenic viruses by the host innate immune system. Recent results from our laboratory show how immune cells use the DNA-sensing machinery to detect intracellular damage generated early during infectio...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.01081-16
更新日期:2017-06-26 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) primary infection is characterized by the use of CCR5 as a coreceptor for viral entry, which is associated with the non-syncytium-inducing (NSI) phenotype in lymphoid cells. Syncytium-inducing (SI) variants of HIV-1 appear in advanced stages of HIV-1 infection and are charac...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.21.10319-10325.2001
更新日期:2001-11-01 00:00:00
abstract:UNLABELLED:To investigate the molecular mechanism(s) by which herpes simplex virus 1 (HSV-1) regulatory protein ICP0 promotes viral gene expression and replication, we screened cells overexpressing ICP0 for ICP0-binding host cell proteins. Tandem affinity purification of transiently expressed ICP0 coupled with mass spe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03043-15
更新日期:2016-01-06 00:00:00
abstract::When ts7, a temperature-sensitive (ts) mutant of influenza B/Kanagawa/73 virus, infected MDCK cells at the nonpermissive temperature (37.5 degrees C), infectious virus was produced at very low levels compared with the yield at the permissive temperature (32 degrees C) and hemagglutinating activity and enzymatic activi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.2.1250-1254.1994
更新日期:1994-02-01 00:00:00
abstract::Spumaviruses, or foamy viruses, express Gag proteins that are incompletely processed by the viral protease in cell cultures. To delineate the proteolytic cleavage sites between potential Gag subdomains, recombinant human spumaretrovirus (HSRV) Gag proteins of different lengths were expressed, purified by affinity chro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.9.7907-7911.1999
更新日期:1999-09-01 00:00:00
abstract::Varicella-zoster virus (VZV) is distinguished from herpes simplex virus type 1 (HSV-1) by the fact that cell-to-cell fusion and syncytium formation require only gH and gL within a transient-expression system. In the HSV system, four glycoproteins, namely, gH, gL, gB, and gD, are required to induce a similar fusogenic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.19.9483-9492.2001
更新日期:2001-10-01 00:00:00
abstract::The complete DNA sequence of bovine adenovirus type 3 is reported here. The size of the genome is 34,446 bp in length with a G+C content of 54%. All the genes of the early and late regions are present in the expected locations of the genome. However, the late-region genes are organized into seven families, instead of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.2.1394-1402.1998
更新日期:1998-02-01 00:00:00
abstract::Growing CV1 cells were infected with simian virus 40 (SV40), and the levels of DNA polymerases-alpha, -beta, and -gamma were analyzed in the cytoplasm, nuclear Triton wash, and nucleus. In the cytoplasmic fraction, the amount of alpha-, beta-, or gamma-polymerase remained unaltered after SV40 infection. The activity o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.23.1.117-125.1977
更新日期:1977-07-01 00:00:00
abstract::H2dl808 is a defective deletion mutant of human adenovirus 2 lacking most of transcriptional early region 4. Although the mutant can be grown in the complementing cell line W162, it is defective in human cell lines normally used to propagate adenovirus. In such nonpermissive cells, H2dl808 exhibits a severe defect in ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.3.833-838.1986
更新日期:1986-03-01 00:00:00
abstract::To examine the contribution of the transmembrane envelope glycoprotein (TM) to the infectivity of the human T-cell leukemia virus type 1 (HTLV-1), single amino acid substitutions were introduced throughout its ectodomain. The mutated envelopes were tested for intracellular maturation and for functions, including abili...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.10.7180-7186.1997
更新日期:1997-10-01 00:00:00
abstract::The mechanism of action of hepatitis B virus (HBV) X protein in transcriptional transactivation and in tumorigenesis remains obscure. We have used the yeast two-hybrid system to identify a cellular protein that can interact with HBV X protein. This protein, designated X-associated protein 1 (XAP-1), is a human homolog...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.2.1107-1114.1995
更新日期:1995-02-01 00:00:00
abstract::A detailed comparison of the gp70 proteins of cloned ecotropic Friend murine leukemia virus (FLV) and dual-tropic Friend mink focus-forming virus (FrMCF) was performed by analyzing the structural and immunological properties of amino- and carboxy-terminal domains of these molecules generated upon controlled trypsiniza...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.2.452-458.1984
更新日期:1984-02-01 00:00:00