Roles of Cholesterol in Early and Late Steps of the Nipah Virus Membrane Fusion Cascade.

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 Virol

journal_title

Journal of virology

authors

Contreras EM,Johnston GP,Buchholz DW,Ortega V,Monreal IA,Zamora JLR,Cheung T,Aguilar HC

doi

10.1128/JVI.02323-20

subject

Has Abstract

pub_date

2021-01-06 00:00:00

eissn

0022-538X

issn

1098-5514

pii

JVI.02323-20

pub_type

杂志文章
  • Picornavirus-specific CD4+ T lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies.

    abstract::Picornaviruses are a family of positive-strand RNA viruses that are responsible for a variety of devastating human and animal diseases. An attenuated strain of mengovirus (vMC24) is serologically indistinguishable from the lethal murine wild-type mengovirus and encephalomyocarditis virus (EMCV). Immunogen-specific sti...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.69.8.4914-4923.1995

    authors: Neal ZC,Splitter GA

    更新日期:1995-08-01 00:00:00

  • Replication of hepatitis A viruses with chimeric 5' nontranslated regions.

    abstract::The role of the 5' nontranslated region in the replication of hepatitis A virus (HAV) was studied by analyzing the translation and replication of chimeric RNAs containing the encephalomyocarditis virus (EMCV) internal ribosome entry segment (IRES) and various lengths (237, 151, or 98 nucleotides [nt]) of the 5'-termin...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.5.2861-2868.1996

    authors: Jia XY,Tesar M,Summers DF,Ehrenfeld E

    更新日期:1996-05-01 00:00:00

  • Impact and regulation of lambda interferon response in human metapneumovirus infection.

    abstract:UNLABELLED:Human metapneumovirus (hMPV) is a respiratory paramyxovirus that is distributed worldwide and induces significant airway morbidity. Despite the relevance of hMPV as a pathogen, many aspects of the immune response to this virus are still largely unknown. In this report, we focus on the antiviral immune respon...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02897-14

    authors: Baños-Lara Mdel R,Harvey L,Mendoza A,Simms D,Chouljenko VN,Wakamatsu N,Kousoulas KG,Guerrero-Plata A

    更新日期:2015-01-01 00:00:00

  • Vaccination of pigs against swine influenza viruses by using an NS1-truncated modified live-virus vaccine.

    abstract::Swine influenza viruses (SIV) naturally infect pigs and can be transmitted to humans. In the pig, genetic reassortment to create novel influenza subtypes by mixing avian, human, and swine influenza viruses is possible. An SIV vaccine inducing cross-protective immunity between different subtypes and strains circulating...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00787-06

    authors: Richt JA,Lekcharoensuk P,Lager KM,Vincent AL,Loiacono CM,Janke BH,Wu WH,Yoon KJ,Webby RJ,Solórzano A,García-Sastre A

    更新日期:2006-11-01 00:00:00

  • Influenza virus hemagglutinin and neuraminidase glycoproteins stimulate the membrane association of the matrix protein.

    abstract::We have analyzed the mechanism by which the matrix (M1) protein associates with cellular membranes during influenza A virus assembly. Interaction of the M1 protein with the viral hemagglutinin (HA) or neuraminidase (NA) glycoprotein was extensively analyzed by using wild-type and transfectant influenza viruses as well...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.10.6653-6657.1996

    authors: Enami M,Enami K

    更新日期:1996-10-01 00:00:00

  • Analysis of the varicella-zoster virus IE62 N-terminal acidic transactivating domain and its interaction with the human mediator complex.

    abstract::The varicella-zoster virus major transactivator, IE62, contains a potent N-terminal acidic transcriptional activation domain (TAD). Our experiments revealed that the minimal IE62 TAD encompasses amino acids (aa) 19 to 67. We showed that the minimal TAD interacts with the human Mediator complex. Site-specific mutations...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00054-09

    authors: Yamamoto S,Eletsky A,Szyperski T,Hay J,Ruyechan WT

    更新日期:2009-06-01 00:00:00

  • The morphology and composition of influenza A virus particles are not affected by low levels of M1 and M2 proteins in infected cells.

    abstract::We generated a recombinant influenza A virus (Mmut) that produced low levels of matrix (M1) and M2 proteins in infected cells. Mmut virus propagated to significantly lower titers than did wild-type virus in cells infected at low multiplicity. By contrast, virion morphology and incorporation of viral proteins and vRNAs...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.12.7926-7932.2005

    authors: Bourmakina SV,García-Sastre A

    更新日期:2005-06-01 00:00:00

  • Close association between shape alteration and loss of immunity to superinfection in a wild-type Klebsiella pneumoniae stable lysogen which can be both immune and nonimmune to superinfection.

    abstract::Klebsiella pneumoniae MirM7 is a wild-type strain which grows as cocci at pH 7 and above and as rods at pH 6.5 and below. Cultures of this strain and an auxotrophic derivative, MirM7b, have been found to undergo spontaneous lysis after purification from possible contaminating viruses. Lysates always contained two phag...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.28.3.772-785.1978

    authors: Satta G,Pruzzo C,Debbia E,Fontana R

    更新日期:1978-12-01 00:00:00

  • Interaction and interdependent packaging of tegument protein UL11 and glycoprotein e of herpes simplex virus.

    abstract::The UL11 tegument protein of herpes simplex virus plays a critical role in the secondary envelopment; however, the mechanistic details remain elusive. Here, we report a new function of UL11 in the budding process in which it directs efficient acquisition of glycoprotein E (gE) via a direct interaction. In vitro bindin...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.05207-11

    authors: Han J,Chadha P,Meckes DG Jr,Baird NL,Wills JW

    更新日期:2011-09-01 00:00:00

  • Effect of number and position of EBNA-1 binding sites in Epstein-Barr virus oriP on the sites of initiation, barrier formation, and termination of replication.

    abstract::DNA replication intermediates of three plasmids containing all or part of a modified Epstein-Barr virus cis-acting plasmid maintenance region (oriP) were examined to further investigate oriP function. Replication intermediates were analyzed in vivo and in vitro by neutral-neutral two-dimensional gel electrophoresis. T...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.67.3.1739-1745.1993

    authors: Platt TH,Tcherepanova IY,Schildkraut CL

    更新日期:1993-03-01 00:00:00

  • PB2 protein of a highly pathogenic avian influenza virus strain A/chicken/Yamaguchi/7/2004 (H5N1) determines its replication potential in pigs.

    abstract::It has been shown that not all but most of the avian influenza viruses replicate in the upper respiratory tract of pigs (H. Kida et al., J. Gen. Virol. 75:2183-2188, 1994). It was shown that A/chicken/Yamaguchi/7/2004 (H5N1) [Ck/Yamaguchi/04 (H5N1)] did not replicate in pigs (N. Isoda et al., Arch. Virol. 151:1267-127...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01879-08

    authors: Manzoor R,Sakoda Y,Nomura N,Tsuda Y,Ozaki H,Okamatsu M,Kida H

    更新日期:2009-02-01 00:00:00

  • Assembly of severe acute respiratory syndrome coronavirus RNA packaging signal into virus-like particles is nucleocapsid dependent.

    abstract::The severe acute respiratory syndrome coronavirus (SARS-CoV) was recently identified as the etiology of SARS. The virus particle consists of four structural proteins: spike (S), small envelope (E), membrane (M), and nucleocapsid (N). Recognition of a specific sequence, termed the packaging signal (PS), by a virus N pr...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.22.13848-13855.2005

    authors: Hsieh PK,Chang SC,Huang CC,Lee TT,Hsiao CW,Kou YH,Chen IY,Chang CK,Huang TH,Chang MF

    更新日期:2005-11-01 00:00:00

  • Identification of amino acid substitutions supporting antigenic change of influenza A(H1N1)pdm09 viruses.

    abstract:UNLABELLED:The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02962-14

    authors: Koel BF,Mögling R,Chutinimitkul S,Fraaij PL,Burke DF,van der Vliet S,de Wit E,Bestebroer TM,Rimmelzwaan GF,Osterhaus AD,Smith DJ,Fouchier RA,de Graaf M

    更新日期:2015-04-01 00:00:00

  • Extracellular vaccinia virus envelope glycoprotein encoded by the A33R gene.

    abstract::With the aid of three monoclonal antibodies (MAbs), a glycoprotein specifically localized to the outer envelope of vaccinia virus was shown to be encoded by the A33R gene. These MAbs reacted with a glycosylated protein that migrated as 23- to 28-kDa and 55-kDa species under reducing and nonreducing conditions, respect...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.6.3753-3762.1996

    authors: Roper RL,Payne LG,Moss B

    更新日期:1996-06-01 00:00:00

  • Poliovirus requires a precise 5' end for efficient positive-strand RNA synthesis.

    abstract::Poliovirus infectious RNA can be synthesized in vitro using phage DNA-dependent RNA-polymerases. These synthetic transcripts contain several extra nucleotides at the 5' end, which are deleted during replication to generate authentic viral genomes. We removed those 5'-end extra nucleotides utilizing a hammerhead ribozy...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.14.6394-6400.2000

    authors: Herold J,Andino R

    更新日期:2000-07-01 00:00:00

  • Functional analysis and structural modeling of human APOBEC3G reveal the role of evolutionarily conserved elements in the inhibition of human immunodeficiency virus type 1 infection and Alu transposition.

    abstract::Retroelements are important evolutionary forces but can be deleterious if left uncontrolled. Members of the human APOBEC3 family of cytidine deaminases can inhibit a wide range of endogenous, as well as exogenous, retroelements. These enzymes are structurally organized in one or two domains comprising a zinc-coordinat...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01491-09

    authors: Bulliard Y,Turelli P,Röhrig UF,Zoete V,Mangeat B,Michielin O,Trono D

    更新日期:2009-12-01 00:00:00

  • Two different molecular defects in the Tva receptor gene explain the resistance of two tvar lines of chickens to infection by subgroup A avian sarcoma and leukosis viruses.

    abstract::The subgroup A to E avian sarcoma and leukosis viruses (ASLVs) are highly related and are thought to have evolved from a common ancestor. These viruses use distinct cell surface proteins as receptors to gain entry into avian cells. Chickens have evolved resistance to infection by the ASLVs. We have identified the muta...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.24.13489-13500.2004

    authors: Elleder D,Melder DC,Trejbalova K,Svoboda J,Federspiel MJ

    更新日期:2004-12-01 00:00:00

  • Integration of proviral DNA in chicken cells infected with Schmidt-Ruppin Rous sarcoma virus is not enhanced by DNA repair.

    abstract::The effect DNA repair might have on the integration of exogenous proviral DNA into host cell DNA was investigated by comparing the efficiency of proviral DNA integration in normal chicken embryonic fibroblasts and in chicken embryonic fibroblasts treated with UV or 4-nitroquinoline-1-oxide. The cells were treated with...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.23.3.533-542.1977

    authors: Tsuruo T,Baluda MA

    更新日期:1977-09-01 00:00:00

  • Phosphorylation of varicella-zoster virus open reading frame (ORF) 62 regulatory product by viral ORF 47-associated protein kinase.

    abstract::Varicella-zoster virus (VZV) encodes within its unique long region a gene product with protein kinase motifs. In a previous study, we demonstrated that immunoprecipitated VZV open reading frame (ORF) 47 protein was associated with a functional protein kinase activity, on the basis of its ability to both autophosphoryl...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.68.3.1350-1359.1994

    authors: Ng TI,Keenan L,Kinchington PR,Grose C

    更新日期:1994-03-01 00:00:00

  • Herpesvirus saimiri Tip-484 membrane protein markedly increases p56lck activity in T cells.

    abstract::Herpesvirus saimiri (HVS) is a T-cell-specific transforming and oncogenic virus. A protein encoded by HVS known as Tip-484 (for tyrosine kinase interacting protein from HVS strain 484) is required for this transformation. Tip-484 binds specifically to the nonreceptor protein tyrosine kinase p56lck. By transfecting Tip...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.71.1.378-382.1997

    authors: Lund T,Medveczky MM,Medveczky PG

    更新日期:1997-01-01 00:00:00

  • Protein Kinase Activity Associated with the Extracellular and Occluded Forms of the Baculovirus Autographa californica Nuclear Polyhedrosis Virus.

    abstract::Protein kinase activity is associated with both the extracellular and the occluded forms of Autographa californica nuclear polyhedrosis virus, a baculovirus. Serine and threonine are the predominant amino acids phosphorylated by the kinase activity associated with both viral forms; no phosphotyrosine was detected. The...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.46.1.275-278.1983

    authors: Miller LK,Adang MJ,Browne D

    更新日期:1983-04-01 00:00:00

  • Inducible MicroRNA-3570 Feedback Inhibits the RIG-I-Dependent Innate Immune Response to Rhabdovirus in Teleost Fish by Targeting MAVS/IPS-1.

    abstract::Effectively recognizing invading viruses and subsequently inducing innate antiviral immunity are essential for host antiviral defense. Although these processes are closely regulated by the host to maintain immune balance, viruses have evolved the ability to downregulate or upregulate these processes for their survival...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01594-17

    authors: Xu T,Chu Q,Cui J,Bi D

    更新日期:2018-01-02 00:00:00

  • Effect of hepatitis C virus (HCV) NS5B-nucleolin interaction on HCV replication with HCV subgenomic replicon.

    abstract::We previously reported that nucleolin, a representative nucleolar marker, interacts with nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) through two independent regions of NS5B, amino acids 208 to 214 and 500 to 506. We also showed that truncated nucleolin that harbors the NS5B-binding region inhibited the ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.80.7.3332-3340.2006

    authors: Shimakami T,Honda M,Kusakawa T,Murata T,Shimotohno K,Kaneko S,Murakami S

    更新日期:2006-04-01 00:00:00

  • Rhesus rhadinovirus infection of rhesus fibroblasts occurs through clathrin-mediated endocytosis.

    abstract::Rhesus rhadinovirus (RRV) is a gammaherpesvirus closely related to Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic virus linked to the development of Kaposi's sarcoma and several other lymphoproliferative diseases, including primary effusion lymphoma and multicentric Castleman's disease. RRV naturally inf...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01429-10

    authors: Zhang W,Zhou F,Greene W,Gao SJ

    更新日期:2010-11-01 00:00:00

  • Global suppression of the host antiviral response by Ebola- and Marburgviruses: increased antagonism of the type I interferon response is associated with enhanced virulence.

    abstract::We studied the effect of filovirus infection on host cell gene expression by characterizing the regulation of gene expression responses in human liver cells infected with Zaire Ebolavirus (ZEBOV), Reston Ebolavirus (REBOV), and Marburgvirus (MARV), using transcriptional profiling and bioinformatics. Expression microar...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.80.6.3009-3020.2006

    authors: Kash JC,Mühlberger E,Carter V,Grosch M,Perwitasari O,Proll SC,Thomas MJ,Weber F,Klenk HD,Katze MG

    更新日期:2006-03-01 00:00:00

  • Heat Shock Protein 90 Ensures Efficient Mumps Virus Replication by Assisting with Viral Polymerase Complex Formation.

    abstract::Paramyxoviral RNAs are synthesized by a viral RNA-dependent RNA polymerase (RdRp) consisting of the large (L) protein and its cofactor phosphoprotein (P protein). The L protein is a multifunctional protein that catalyzes RNA synthesis, mRNA capping, and mRNA polyadenylation. Growing evidence shows that the stability o...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02220-16

    authors: Katoh H,Kubota T,Nakatsu Y,Tahara M,Kidokoro M,Takeda M

    更新日期:2017-02-28 00:00:00

  • Identification and expression analysis of herpes B virus-encoded small RNAs.

    abstract::Herpes B virus (BV) naturally infects macaque monkeys and is genetically similar to herpes simplex virus (HSV). Zoonotic infection of humans can cause encephalitis and if untreated has a fatality rate of ∼80%. The frequent use of macaques in biomedical research emphasizes the need to understand the molecular basis of ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00505-11

    authors: Amen MA,Griffiths A

    更新日期:2011-07-01 00:00:00

  • A point mutation abolishes the helicase but not the nucleoside triphosphatase activity of hepatitis C virus NS3 protein.

    abstract::The NS3 protein of hepatitis C virus contains a bipartite structure consisting of an N-terminal serine protease and a C-terminal DEAD box helicase. We show that the C-terminal domain has ATPase and panhelicase activities. The integrity of the helicase function is dependent on the conserved DEAD motif and can be abolis...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.71.8.6264-6266.1997

    authors: Heilek GM,Peterson MG

    更新日期:1997-08-01 00:00:00

  • The genome sequence of the emerging common midwife toad virus identifies an evolutionary intermediate within ranaviruses.

    abstract::Worldwide amphibian population declines have been ascribed to global warming, increasing pollution levels, and other factors directly related to human activities. These factors may additionally be favoring the emergence of novel pathogens. In this report, we have determined the complete genome sequence of the emerging...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.07108-11

    authors: Mavian C,López-Bueno A,Balseiro A,Casais R,Alcamí A,Alejo A

    更新日期:2012-04-01 00:00:00

  • Isolation and preliminary characterization of bacteriophages for Bdellovibrio bacteriovorus.

    abstract::Ten bacteriophages that attack and lyse saprophytic strains of Bdellovibrio bacteriovorus were isolated. Morphological, serological, and host-range studies revealed that there were four different bdellovibrio phages present among the isolates. One of the phages lysed a strain of B. bacteriovorus that requires the pres...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.10.3.516-523.1972

    authors: Althauser M,Samsonoff WA,Anderson C,Conti SF

    更新日期:1972-09-01 00:00:00