Abstract:
:Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) is a cytokine that is poorly secreted and localized largely to the endoplasmic reticulum (ER). It has been implicated, along with other HHV-8 proinflammatory and/or angiogenic viral proteins, in HHV-8-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), in addition to an MCD-related disorder involving systemic elevation of proinflammatory cytokines, including vIL-6 and human IL-6 (hIL-6). In these diseases, lytic (productive) replication, in addition to viral latency, is believed to play a critical role. Proreplication activity of vIL-6 has been identified experimentally in PEL and endothelial cells, but the relative contributions of different vIL-6 interactions have not been established. Productive interactions of vIL-6 with the IL-6 signal transducer, gp130, can occur within the ER, but vIL-6 also interacts in the ER with a nonsignaling receptor called vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2), calnexin, and VKORC1v2- and calnexin-associated proteins UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) and glucosidase II (GlucII). Here, we report the systematic characterization of interaction-altered vIL-6 variants and the lytic phenotypes of recombinant viruses expressing selected variants. Our data identify the critical importance of vIL-6 and its ER-localized activity via gp130 to productive replication in inducible SLK (epithelial) cells, absence of detectable involvement of vIL-6 interactions with VKORC1v2, GlucII, or UGGT1, and the insufficiency and lack of direct contributory effects of extracellular signaling by vIL-6 or hIL-6. These findings, obtained through genetics-based approaches, complement and extend previous analyses of vIL-6 activity.IMPORTANCE Human herpesvirus 8 (HHV-8)-encoded viral interleukin-6 (vIL-6) was the first viral IL-6 homologue to be identified. Experimental and clinical evidence suggests that vIL-6 is important for the onset and/or progression of HHV-8-associated endothelial-cell and B-cell pathologies, including AIDS-associated Kaposi's sarcoma and multicentric Castleman's disease. The protein is unusual in its poor secretion from cells and its intracellular activity; it interacts, directly or indirectly, with a number of proteins beyond the IL-6 signal transducer, gp130, and can mediate activities through these interactions in the endoplasmic reticulum. Here, we report the characterization with respect to protein interactions and signal-transducing activity of a panel of vIL-6 variants and utilization of HHV-8 mutant viruses expressing selected variants in phenotypic analyses. Our findings establish the importance of vIL-6 in HHV-8 productive replication and the contributions of individual vIL-6-protein interactions to HHV-8 lytic biology. This work furthers understanding of the biological significance of vIL-6 and its unique intracellular interactions.
journal_name
J Viroljournal_title
Journal of virologyauthors
Li Q,Xiang Q,Chen D,Nicholas Jdoi
10.1128/JVI.00909-20subject
Has Abstractpub_date
2020-09-15 00:00:00issue
19eissn
0022-538Xissn
1098-5514pii
JVI.00909-20journal_volume
94pub_type
杂志文章abstract::The effect of guanidine on the replication of the group A arboviruses, Sindbis virus, and Semliki Forest virus (SFV) was studied. Guanidine rapidly, but reversibly, inhibited SFV ribonucleic acid (RNA) synthesis. The synthesis of all species of viral RNA was inhibited, but that of ribonuclease-resistant forms was leas...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.6.5.628-636.1970
更新日期:1970-11-01 00:00:00
abstract::Varicella-zoster virus (VZV) DNA was prepared from nucleocapsids and from enveloped virions of a laboratory strain (Ellen) and directly from the vesicle fluids of patients with zoster infections. VZV Ellen nucleocapsid DNA was cleaved with 11 different restriction endonucleases and electrophoresed in agarose gels. The...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.40.2.516-525.1981
更新日期:1981-11-01 00:00:00
abstract::A Sepharose 4B chromatographic method for purification of retroviruses is described which was less time consuming, increased purified virus yields, conserved viral glycoprotein, and increased recovery of biological infectivity in comparison with conventional sucrose gradient ultracentrifugation techniques. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.25.3.923-927.1978
更新日期:1978-03-01 00:00:00
abstract::We examined the 5' ends of Hantaan virus (HTN) genomes and mRNAs to gain insight into the manner in which these chains were initiated. Like those of all members of the family Bunyaviridae described so far, the HTN mRNAs contained 5' terminal extensions that were heterogeneous in both length and sequence, presumably be...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5754-5762.1995
更新日期:1995-09-01 00:00:00
abstract::The small defective T particle of vesicular stomatitis virus (VSV-111) has no detectable enzyme activity when assayed at 31 C, although qualitatively it possesses all the virion proteins found in complete VSV-1 virions. With VSV-1 transcription product ribonucleic acid (RNA), it is shown that the VSV-111 RNA is identi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.6.946-955.1972
更新日期:1972-06-01 00:00:00
abstract::Transient CD154 blockade at the onset of Theiler's murine encephalomyelitis virus-induced demyelinating disease ameliorated disease progression for 80 days, reduced immune cell infiltration, and transiently increased viral loads in the central nervous system. Peripheral antiviral and autoimmune T-cell responses were n...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.3.2247-2250.2003
更新日期:2003-02-01 00:00:00
abstract::Primary HIV-1 infection (PHI) is marked by a flu-like syndrome and high levels of viremia that decrease to a viral set point with the first emergence of virus-specific CD8+ T-cell responses. Here, we investigated in a large cohort of 527 subjects the immunodominance pattern of the first virus-specific cytotoxic T-lymp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00182-09
更新日期:2009-08-01 00:00:00
abstract::Knowledge of the mechanisms of virus dissemination in acute measles is cursory, but cells of the monocyte/macrophage (MM) lineage appear to be early targets. We characterized the dissemination of the Edmonston B vaccine strain of measles virus (MV-Ed) in peripheral blood mononuclear cells (PBMC) of two mouse strains e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.7.3343-3351.2001
更新日期:2001-04-01 00:00:00
abstract::Luteoviruses and the luteovirus-like pea enation mosaic virus (PEMV; genus Enamovirus) are transmitted by aphids in a circulative, nonreplicative manner. Acquired virus particles persist for several weeks in the aphid hemolymph, in which a GroEL homolog, produced by the primary endosymbiont of the aphid, is abundantly...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.10.7258-7265.1997
更新日期:1997-10-01 00:00:00
abstract::Hamster cells are completely nonpermissive for the replication of human adenovirus type 12 (Ad12), whereas types 2 and 5 can replicate in hamster cells. The Ad5-transformed hamster cell line BHK297-C131, which carries the left terminal 18.7% of the Ad5 genome and expresses at least the viral E1A region, can somehow co...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.5476-5482.1994
更新日期:1994-09-01 00:00:00
abstract::Expression of the human ADA cDNA encoded by the Moloney murine leukemia virus spliced RNA form is enhanced by intron-contained sequences. The presence of sequences corresponding to the viral gag gene in a Moloney murine leukemia virus-based vector results in the generation of 10- to 40-fold higher titers of virus. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.5.1647-1650.1987
更新日期:1987-05-01 00:00:00
abstract::Isoelectrofocusing of nonionic-detergent-disrupted flaviviruses separated the envelope glycoprotein of 53,000 to 58,000 daltons and the nucleocapsid protein of 14,000 daltons. The envelope protein and nucleocapsid protein were isolated at isoelectric points of pI 7.8 and 10.3, respectively. The antigenic determinants ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.22.3.608-618.1977
更新日期:1977-06-01 00:00:00
abstract:UNLABELLED:Hepatitis C virus (HCV) requires proteins from the NS3-NS5B polyprotein to create a replicase unit for replication of its genome. The replicase proteins form membranous compartments in cells to facilitate replication, but little is known about their functional organization within these structures. We recentl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01931-15
更新日期:2015-12-30 00:00:00
abstract::Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes simplex virus (HSV) infect...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01167-07
更新日期:2007-12-01 00:00:00
abstract::The human genome encodes over 500 microRNAs (miRNAs), small RNAs (19 to 26 nucleotides [nt]) that regulate the expressions of diverse cellular genes. Many cellular processes are altered through a variety of mechanisms by human cytomegalovirus (HCMV) infection. We asked whether HCMV infection leads to changes in the ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00961-08
更新日期:2008-09-01 00:00:00
abstract::All known DNA tumor viruses are known to target and inactivate two main cell cycle regulatory proteins, retinoblastoma protein (pRb) and p53. Inactivation of pRb promotes host cell cycle progression into S phase, and inactivation of p53 promotes cell immortalization. The DNA tumor virus Kaposi's sarcoma associated her...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.19.10336-10347.2004
更新日期:2004-10-01 00:00:00
abstract::The restrictive properties of tripartite motif-containing 5 alpha (TRIM5α) from small ruminant species have not been explored. Here, we identify highly similar TRIM5α sequences in sheep and goats. Cells transduced with ovine TRIM5α effectively restricted the lentivirus visna/maedi virus DNA synthesis. Proteasome inhib...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00440-12
更新日期:2012-09-01 00:00:00
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
doi:10.1128/JVI.01144-12
更新日期:2012-10-01 00:00:00
abstract::Type I interferons (IFNs), as major components of the innate immune system, play a vital role in host resistance to a variety of pathogens. Canonical signaling mediated by type I IFNs activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway through binding to the IFN-α/β receptor ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01161-18
更新日期:2018-09-12 00:00:00
abstract::Recombinant Epstein-Barr virus (EBV) with a selectable marker successfully infected the human gastric carcinoma cell lines AGS, MKN28, and MKN74. Following incubation in selective media, drug-resistant cell clones were isolated and proved to be infected with EBV. All gastric carcinoma cell clones were positive for EBN...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.7.5688-5691.1997
更新日期:1997-07-01 00:00:00
abstract::Infection of monkey cells with human adenovirus (Ad) is abortive, but the infection can be enhanced by coinfecting with simian virus 40 (SV40). However, in the coinfected monkey cells, Ad interferes strongly with SV40 DNA biosynthesis. This interference was found to be a reproducible, delicately controlled phenomenon ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.27.2.275-287.1978
更新日期:1978-08-01 00:00:00
abstract::Approximately 10% of gastric carcinomas (GC) are comprised of cells latently infected with Epstein-Barr virus (EBV); however, the mechanism by which EBV contributes to the development of this malignancy is unclear. We have investigated the cellular effects of the only EBV nuclear protein expressed in GC, EBNA1, focusi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05623-11
更新日期:2012-01-01 00:00:00
abstract::Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) was modified to encode targeting signals known to localize proteins to either the endoplasmic reticulum (ER) or the trans-Golgi network. These motifs conferred the predicted targeting properties on gD in transfected cells as judged by immunofluorescence staini...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9515-9520.1999
更新日期:1999-11-01 00:00:00
abstract::We evaluated the ability of human coronaviruses to infect primary cultures of human neural cells. Double immunofluorescence with antibodies to virus and cell markers showed infection of fetal astrocytes and of adult microglia and astrocytes by strain OC43. RNA amplification revealed infection of fetal astrocytes, adul...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.1.800-806.1997
更新日期:1997-01-01 00:00:00
abstract:UNLABELLED:Numerous experimental studies have demonstrated that CD8(+) T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8(+) T cells. Here we use a n...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01571-15
更新日期:2015-11-01 00:00:00
abstract::The present study was designed to investigate the endocytic pathway involved in canine parvovirus (CPV) infection. Reduced temperature (18 degrees C) or the microtubule-depolymerizing drug nocodazole was found to inhibit productive infection of canine A72 cells by CPV and caused CPV to be retained in cytoplasmic vesic...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.1.802-806.1998
更新日期:1998-01-01 00:00:00
abstract::Human cytomegalovirus (HCMV) has been implicated as a potential cofactor in human immunodeficiency virus type 1 (HIV-1)-related disease. Previously, we reported that HCMV inhibits HIV-1 RNA and protein synthesis in cells productively infected with both viruses but, in transient assays, activates an HIV-1 long terminal...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.3.1645-1651.1995
更新日期:1995-03-01 00:00:00
abstract::The multistranded and double-stranded RNAs synthesized in HeLa cells infected with rhinovirus in the presence and in the absence of actinomycin D have been characterized by polyacrylamide gel electrophoresis and hybridization studies. The replicative form is only found in infected cells treated with actinomycin D, whe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.3.926-932.1976
更新日期:1976-06-01 00:00:00
abstract::Thirteen dengue virus-specific, cytotoxic CD4+ CD8- T-cell clones were established from a donor who was infected with dengue virus type 3. These clones were examined for virus specificity and human leukocyte antigen (HLA) restriction in cytotoxic assays. Six patterns of virus specificities were determined. Two serotyp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.4.1823-1828.1991
更新日期:1991-04-01 00:00:00
abstract::There is a high degree of intraisolate sequence heterogeneity in the tax gene of human T-cell leukemia virus type I (HTLV-I), although the sequence variation between patients is small compared with that of human immunodeficiency virus type 1. In the present study, we investigated whether naturally occurring amino acid...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.4.2649-2653.1995
更新日期:1995-04-01 00:00:00