Role of Sphingomyelin in Alphaherpesvirus Entry.


:Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes disease in cattle populations worldwide. Sphingomyelin (SM) is the most abundant sphingolipid in the mammalian cell membrane, where it preferentially associates with cholesterol to form lipid raft domains. SM is a substrate for the lysosome-resident enzyme acid sphingomyelinase, which plays a role in cell membrane repair following injury. Treatment of cells with noncytotoxic concentrations of Staphylococcus aureus-derived sphingomyelinase successfully reduced cell surface-exposed sphingomyelin but did not significantly inhibit BoHV-1 entry and infection, as measured by the beta-galactosidase reporter assay. Interestingly, entry of the porcine alphaherpesvirus pseudorabies virus (PRV) was inhibited by sphingomyelin-depletion of cells. Treatment of BoHV-1 particles with sphingomyelinase inhibited viral entry activity, suggesting that viral SM plays a role in BoHV-1 entry, while cellular SM does not. Treatment of cells with noncytotoxic concentrations of the functional inhibitors of host acid sphingomyelinase, imipramine and amitriptyline, which induce degradation of the cellular enzyme, did not significantly inhibit BoHV-1 entry. In contrast, inhibition of cellular acid sphingomyelinase inhibited PRV entry. Entry of the human alphaherpesvirus herpes simplex virus 1 (HSV-1) was independent of both host SM and acid sphingomyelinase, in a manner similar to BoHV-1. Together, the results suggest that among the alphaherpesviruses, there is variability in entry requirements for cellular sphingomyelin and acid sphingomyelinase activity.IMPORTANCE Bovine herpesvirus 1 (BoHV-1) is an ubiquitous pathogen affecting cattle populations worldwide. Infection can result in complicated, polymicrobial infections due to the immunosuppressive properties of the virus. Available vaccines limit disease severity and spread but do not prevent infection. The financial and animal welfare ramifications of BoHV-1 are significant. In order to develop more effective prevention and treatment regimens, a more complete understanding of the initial steps in viral infection is necessary. We recently identified a low pH endocytosis pathway for BoHV-1. Here, we examine the role of cellular factors responsible for membrane integrity and repair in alphaherpesviral entry. This study allows comparisons of the BoHV-1 entry pathway with those of other alphaherpesviruses (pseudorabies virus [PRV] and herpes simplex virus 1 [HSV-1]). Lastly, this is the first report of sphingomyelin and lysosomal sphingomyelinase playing a role in the entry of a herpesvirus. The results may lead to the development of more effective prevention and treatment regimens.


J Virol


Journal of virology


Pastenkos G,Miller JL,Pritchard SM,Nicola AV




Has Abstract


2019-02-19 00:00:00












  • Ancient adaptive evolution of tetherin shaped the functions of Vpu and Nef in human immunodeficiency virus and primate lentiviruses.

    abstract::Tetherin/BST-2 is a host-encoded protein that restricts a wide diversity of viruses at the stage of virion release. However, viruses have evolved antagonists of Tetherin, including the Vpu and Nef proteins of primate lentiviruses. Like other host genes subject to viral antagonism, primate Tetherin genes have evolved u...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Lim ES,Malik HS,Emerman M

    更新日期:2010-07-01 00:00:00

  • Translation of murine leukemia virus RNA in cell-free systems from animal cells.

    abstract::The virion RNA of Moloney murine leukemia virus (MuLV) has been translated in eukaryotic cell-free systems derived from mouse L- and human HeLa cells. In both systems at least three polypeptides, approximately 60,000, 70,000, and 180,000 in apparent molecular weight, were formed in response to the added 35S MuLV RNA. ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kerr IM,Olshevsky U,Lodish HF,Baltimore D

    更新日期:1976-05-01 00:00:00

  • Origin and metabolic properties of the RNA species formed during the replication cycle of virus 2C.

    abstract::When short pulses of [(3)H]uracil were administered to Bacillus subtilis infected with phage 2C, the main species of labeled RNA was a 10S component that hybridized chiefly, but not exclusively, with the heavy strand of 2C DNA. After long pulses, most of the radioactivity was found in the 23S, 16S, and 5S rRNA's, whic...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Cocito C

    更新日期:1974-12-01 00:00:00

  • Two Conserved Amino Acids within the NSs of Severe Fever with Thrombocytopenia Syndrome Phlebovirus Are Essential for Anti-interferon Activity.

    abstract::The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) sequesters TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures to inhibit the phosphorylation and nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3) and subsequent interferon beta (IFN-...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Moriyama M,Igarashi M,Koshiba T,Irie T,Takada A,Ichinohe T

    更新日期:2018-09-12 00:00:00

  • Adult AIDS-like disease in a novel inducible human immunodeficiency virus type 1 Nef transgenic mouse model: CD4+ T-cell activation is Nef dependent and can occur in the absence of lymphophenia.

    abstract::CD4C/HIV(nef) transgenic (Tg) mice express Nef in CD4+ T cells and in the cells of the macrophage/monocyte/dendritic lineage, and they develop an AIDS-like disease similar to human AIDS. In these mice, Nef is constitutively expressed throughout life. To rule out the contribution of any developmental defects caused by ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Rahim MM,Chrobak P,Hu C,Hanna Z,Jolicoeur P

    更新日期:2009-11-01 00:00:00

  • Regulated expression of a Sindbis virus replicon by herpesvirus promoters.

    abstract::We describe the use of herpesvirus promoters to regulate the expression of a Sindbis virus replicon (SINrep/LacZ). We isolated cell lines that contain the cDNA of SINrep/LacZ under the control of a promoter from a herpesvirus early gene which requires regulatory proteins encoded by immediate-early genes for expression...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Ivanova L,Schlesinger S,Olivo PD

    更新日期:1999-03-01 00:00:00

  • Analysis of cytoplasmic RNA and polyribosmomes from feline leukemia virus-infected cells.

    abstract::Cytoplasmic virus-specific RNA and polyribosomes from a chronically infected feline thymus tumor cell line, F-422, were analyzed by using in vitro-synthesized feline leukemia virus (Rickard strain) (R-FeLV) complementary DNA (cDNA) probe. By hybridization kinetics analysis, cytoplasmic, polyribosomat, and nuclear RNAs...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Conely AJ,Velicer LF

    更新日期:1978-03-01 00:00:00

  • Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein.

    abstract::The NS5A protein of hepatitis C virus (HCV) plays an important but undefined role in viral RNA replication. NS5A has been proposed to be a three-domain protein, and the crystal structure of the well-conserved amino-terminal domain I has been determined. The remaining two domains of NS5A, designated domains II and III,...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Tellinghuisen TL,Foss KL,Treadaway JC,Rice CM

    更新日期:2008-02-01 00:00:00

  • The double-stranded RNA genome segments of cytoplasmic polyhedrosis virus are independently transcribed.

    abstract::The in vitro transcription of the genome segments of insect cytoplasmic polyhedrosis virus was examined for a possible mechanism of coordinate control. Initiation of the first transcription cycle, primed by preincubation in the absence of CTP, was synchronous for all 10 viral genome segments. The time required for the...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Smith RE,Furuichi Y

    更新日期:1982-01-01 00:00:00

  • The bean pod mottle virus RNA2-encoded 58-kilodalton protein P58 is required in cis for RNA2 accumulation.

    abstract:UNLABELLED:Bean pod mottle virus (BPMV) is a bipartite, positive-sense (+) RNA plant virus in the Secoviridae family. Its RNA1 encodes proteins required for genome replication, whereas RNA2 primarily encodes proteins needed for virion assembly and cell-to-cell movement. However, the function of a 58-kDa protein (P58) e...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Lin J,Guo J,Finer J,Dorrance AE,Redinbaugh MG,Qu F

    更新日期:2014-03-01 00:00:00

  • HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function.

    abstract::Functional defects in cytotoxic CD8(+) T cell responses arise in chronic human viral infections, but the mechanisms involved are not well understood. In mice, CD4 cell-mediated interleukin-21 (IL-21) production is necessary for the maintenance of CD8(+) T cell function and control of persistent viral infections. To in...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Chevalier MF,Jülg B,Pyo A,Flanders M,Ranasinghe S,Soghoian DZ,Kwon DS,Rychert J,Lian J,Muller MI,Cutler S,McAndrew E,Jessen H,Pereyra F,Rosenberg ES,Altfeld M,Walker BD,Streeck H

    更新日期:2011-01-01 00:00:00

  • Strandedness and complementarity of DNA from long-term RNA-dependent DNA polymerase reactions of Soehner-Dmochowski murine sarcoma virus.

    abstract::The DNA product of the endogenously instructed RNA-dependent DNA polymerase reaction of murine sarcoma virus continued to be synthesized for as long as 64 h in the presence of 0.008% Triton X-100. Higher detergent concentrations and actinomycin D inhibited DNA product synthesis. The DNA product from long-term polymera...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: East JL,Knesek JE,Allen PT,Dmochowski L

    更新日期:1973-11-01 00:00:00

  • Nef-induced CD4 endocytosis in human immunodeficiency virus type 1 host cells: role of p56lck kinase.

    abstract::Human immunodeficiency virus type 1 (HIV-1) Nef interferes with the endocytic machinery to modulate the cell surface expression of CD4. However, the basal trafficking of CD4 is governed by different rules in the target cells of HIV-1: whereas CD4 is rapidly internalized from the cell surface in myeloid cells, CD4 is s...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Laguette N,Brégnard C,Bouchet J,Benmerah A,Benichou S,Basmaciogullari S

    更新日期:2009-07-01 00:00:00

  • Monoclonal antibodies that disrupt poliovirus only at fever temperatures.

    abstract::Three of thirty-six monoclonal antibodies were found to cause irreversible inactivation of type 1 poliovirus at 39 degrees C but not at 37 degrees C. Neutralization at 37 degrees C depended on aggregation and was reversible by acid-induced deaggregation; at 39 degrees C, the virions (N antigenic, 160S) were disrupted ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Delaet I,Boeyé A

    更新日期:1993-09-01 00:00:00

  • Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage.

    abstract::Hemorrhage is a common clinical manifestation in dengue patients. However, the pathogenic mechanism of dengue virus (DV)-induced hemorrhage awaits clarification. We established a mouse model of DV hemorrhage using immunocompetent C57BL/6 mice by injecting DV serotype 2 strain 16681 intradermally. While inoculation of ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Chen HC,Hofman FM,Kung JT,Lin YD,Wu-Hsieh BA

    更新日期:2007-06-01 00:00:00

  • Reverse genetics recovery of Lujo virus and role of virus RNA secondary structures in efficient virus growth.

    abstract::Arenaviruses are rodent-borne viruses with a bisegmented RNA genome. A genetically unique arenavirus, Lujo virus, was recently discovered as the causal agent of a nosocomial outbreak of acute febrile illness with hemorrhagic manifestations in Zambia and South Africa. The outbreak had a case fatality rate of 80%. A rev...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Bergeron É,Chakrabarti AK,Bird BH,Dodd KA,McMullan LK,Spiropoulou CF,Nichol ST,Albariño CG

    更新日期:2012-10-01 00:00:00

  • Transformation-deficient adenovirus mutant defective in expression of region 1A but not region 1B.

    abstract::A adenovirus type 5 host range mutant (hr440) has been isolated which is defective in a splicing event required to generate the middle-sized mRNA from early region 1A. This defect has been ascribed to two adjacent nucleotide changes which lie five and six nucleotides from the 5' splice site for this mRNA (Solnick, Nat...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Solnick D,Anderson MA

    更新日期:1982-04-01 00:00:00

  • Presentation of native epitopes in the V1/V2 and V3 regions of human immunodeficiency virus type 1 gp120 by fusion glycoproteins containing isolated gp120 domains.

    abstract::The immune response to viral glycoproteins is often directed against conformation- and/or glycosylation-dependent structures; synthetic peptides and bacterially expressed proteins are inadequate probes for the mapping of such epitopes. This report describes a retroviral vector system that presents such native epitopes...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kayman SC,Wu Z,Revesz K,Chen H,Kopelman R,Pinter A

    更新日期:1994-01-01 00:00:00

  • The myxoma virus m-t5 ankyrin repeat host range protein is a novel adaptor that coordinately links the cellular signaling pathways mediated by Akt and Skp1 in virus-infected cells.

    abstract::Most poxviruses express multiple proteins containing ankyrin (ANK) repeats accounting for a large superfamily of related but unique determinants of poxviral tropism. Recently, select members of this novel family of poxvirus proteins have drawn considerable attention for their potential roles in modulating intracellula...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Werden SJ,Lanchbury J,Shattuck D,Neff C,Dufford M,McFadden G

    更新日期:2009-12-01 00:00:00

  • Egress of varicella-zoster virus from the melanoma cell: a tropism for the melanocyte.

    abstract::The pathway of envelopment and egress of the varicella-zoster virus (VZV) and the primary site of viral production within the epidermal layer of the skin are not fully understood. There are several hypotheses to explain how the virus may receive an envelope as it travels to the surface of the monolayer. In this study,...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Harson R,Grose C

    更新日期:1995-08-01 00:00:00

  • Immunoglobulin with High-Titer In Vitro Cross-Neutralizing Hepatitis C Virus Antibodies Passively Protects Chimpanzees from Homologous, but Not Heterologous, Challenge.

    abstract::The importance of neutralizing antibodies (NAbs) in protection against hepatitis C virus (HCV) remains controversial. We infused a chimpanzee with H06 immunoglobulin from a genotype 1a HCV-infected patient and challenged with genotype strains efficiently neutralized by H06 in vitro. Genotype 1a NAbs afforded no protec...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Bukh J,Engle RE,Faulk K,Wang RY,Farci P,Alter HJ,Purcell RH

    更新日期:2015-09-01 00:00:00

  • The Antagonism of HIV-1 Nef to SERINC5 Particle Infectivity Restriction Involves the Counteraction of Virion-Associated Pools of the Restriction Factor.

    abstract::SERINC3 (serine incorporator 3) and SERINC5 are recently identified host cell inhibitors of HIV-1 particle infectivity that are counteracted by the viral pathogenesis factor Nef. Here we confirm that HIV-1 Nef, but not HIV-1 Vpu, antagonizes the particle infectivity restriction of SERINC5. SERINC5 antagonism occurred ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Trautz B,Pierini V,Wombacher R,Stolp B,Chase AJ,Pizzato M,Fackler OT

    更新日期:2016-11-14 00:00:00

  • Evolution of feline leukemia virus variant genomes with insertions, deletions, and defective envelope genes in infected cats with tumors.

    abstract::In order to study retroviral variation, selection, and viral correlates of in vivo pathogenicity, we documented the evolution of feline leukemia virus (FeLV) variants in cats that died with thymic lymphoma after infection with molecularly cloned subgroup A FeLV. Using genomic DNA from cat necropsy samples, we employed...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Rohn JL,Linenberger ML,Hoover EA,Overbaugh J

    更新日期:1994-04-01 00:00:00

  • E4orf6 variants with separate abilities to augment adenovirus replication and direct nuclear localization of the E1B 55-kilodalton protein.

    abstract::The E4orf6 protein of group C adenovirus is an oncoprotein that, in association with the E1B 55-kDa protein and by E1B-independent means, promotes virus replication. An arginine-faced amphipathic alpha-helix in the E4orf6 protein is required for the E4orf6 protein to direct nuclear localization of the E1B 55-kDa prote...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Orlando JS,Ornelles DA

    更新日期:2002-02-01 00:00:00

  • Cloning of the full-length rhesus cytomegalovirus genome as an infectious and self-excisable bacterial artificial chromosome for analysis of viral pathogenesis.

    abstract::Rigorous investigation of many functions encoded by cytomegaloviruses (CMVs) requires analysis in the context of virus-host interactions. To facilitate the construction of rhesus CMV (RhCMV) mutants for in vivo studies, a bacterial artificial chromosome (BAC) containing an enhanced green fluorescent protein (EGFP) cas...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Chang WL,Barry PA

    更新日期:2003-05-01 00:00:00

  • An exonic splicing silencer downstream of the 3' splice site A2 is required for efficient human immunodeficiency virus type 1 replication.

    abstract::Alternative splicing of the human immunodeficiency virus type 1 (HIV-1) genomic mRNA produces more than 40 unique viral mRNA species, of which more than half remain incompletely spliced within an HIV-1-infected cell. Regulation of splicing at HIV-1 3' splice sites (3'ss) requires suboptimal polypyrimidine tracts, and ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Madsen JM,Stoltzfus CM

    更新日期:2005-08-01 00:00:00

  • Dexamethasone stimulates expression of transposable type A intracisternal retroviruslike genes in mouse (Mus musculus) cells.

    abstract::Dexamethasone treatment enhances expression of transposable intracisternal type A particles (IAP) at RNA and proteins levels in a murine retrovirus-transformed cell line (Ki-BALB). This effect was ascertained by electron microscopic numeration of IAP. By sequence comparison, we located glucocorticoid-responsive elemen...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Emanoil-Ravier R,Mercier G,Canivet M,Garcette M,Lasneret J,Peronnet F,Best-Belpomme M,Peries J

    更新日期:1988-10-01 00:00:00

  • The Sfpi-1 proviral integration site of Friend erythroleukemia encodes the ets-related transcription factor Pu.1.

    abstract::Previous studies identified a common site (Sfpi-1) for proviral integration in immortalized Friend erythroleukemias. cDNAs corresponding to a 1.5-kb Sfpi-1 mRNA were isolated and sequenced. These were larger than an independently isolated Sfpi-1 cDNA described by researchers from another laboratory, and they contained...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Paul R,Schuetze S,Kozak SL,Kozak CA,Kabat D

    更新日期:1991-01-01 00:00:00

  • Functional entry of baculovirus into insect and mammalian cells is dependent on clathrin-mediated endocytosis.

    abstract::Entry of the budded virus form of baculoviruses into insect and mammalian cells is generally thought to occur through a low-pH-dependent endocytosis pathway, possibly through clathrin-coated pits. This insight is primarily based on (immuno)electron microscopy studies but requires biochemical support to exclude the use...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Long G,Pan X,Kormelink R,Vlak JM

    更新日期:2006-09-01 00:00:00

  • Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical.

    abstract::Dengue virus (DEN) causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease are neither well understood nor easy to examine in humans. In this study, we used wild-type and cong...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Shresta S,Kyle JL,Snider HM,Basavapatna M,Beatty PR,Harris E

    更新日期:2004-03-01 00:00:00