Pattern recognition receptor MDA5 modulates CD8+ T cell-dependent clearance of West Nile virus from the central nervous system.


:Many viruses induce type I interferon responses by activating cytoplasmic RNA sensors, including the RIG-I-like receptors (RLRs). Although two members of the RLR family, RIG-I and MDA5, have been implicated in host control of virus infection, the relative role of each RLR in restricting pathogenesis in vivo remains unclear. Recent studies have demonstrated that MAVS, the adaptor central to RLR signaling, is required to trigger innate immune defenses and program adaptive immune responses, which together restrict West Nile virus (WNV) infection in vivo. In this study, we examined the specific contribution of MDA5 in controlling WNV in animals. MDA5(-/-) mice exhibited enhanced susceptibility, as characterized by reduced survival and elevated viral burden in the central nervous system (CNS) at late times after infection, even though small effects on systemic type I interferon response or viral replication were observed in peripheral tissues. Intracranial inoculation studies and infection experiments with primary neurons ex vivo revealed that an absence of MDA5 did not impact viral infection in neurons directly. Rather, subtle defects were observed in CNS-specific CD8(+) T cells in MDA5(-/-) mice. Adoptive transfer into recipient MDA5(+/+) mice established that a non-cell-autonomous deficiency of MDA5 was associated with functional defects in CD8(+) T cells, which resulted in a failure to clear WNV efficiently from CNS tissues. Our studies suggest that MDA5 in the immune priming environment shapes optimal CD8(+) T cell activation and subsequent clearance of WNV from the CNS.


J Virol


Journal of virology


Lazear HM,Pinto AK,Ramos HJ,Vick SC,Shrestha B,Suthar MS,Gale M Jr,Diamond MS




Has Abstract


2013-11-01 00:00:00














  • Multiple regions in the Rous sarcoma virus src gene intron act in cis to affect the accumulation of unspliced RNA.

    abstract::Retrovirus replication requires the production of both spliced and unspliced viral RNA from a single RNA transcript. In contrast, cellular RNA precursors with introns almost completely spliced. The cis elements and virus-coded trans factors which determine the extent to which Rous sarcoma virus RNA is spliced to src m...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Stoltzfus CM,Fogarty SJ

    更新日期:1989-04-01 00:00:00

  • Human immunodeficiency virus type 1 env trimer immunization of macaques and impact of priming with viral vector or stabilized core protein.

    abstract::Currently there is limited information about the quality of immune responses elicited by candidate human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)-based immunogens in primates. Here we describe a comprehensive analysis of neutralizing antibody and T-cell responses obtained in cynomolgus macaque...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Mörner A,Douagi I,Forsell MN,Sundling C,Dosenovic P,O'Dell S,Dey B,Kwong PD,Voss G,Thorstensson R,Mascola JR,Wyatt RT,Karlsson Hedestam GB

    更新日期:2009-01-01 00:00:00

  • The repressing and enhancing functions of the herpes simplex virus regulatory protein ICP27 map to C-terminal regions and are required to modulate viral gene expression very early in infection.

    abstract::The phenotypic properties of ICP27 temperature-sensitive and deletion mutants and the results of transient expression assays have demonstrated that ICP27 has a modulatory effect on viral gene expression induced by ICPs 0 and 4. In order to identify the regions of the ICP27 molecule that are responsible for its enhanci...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: McMahan L,Schaffer PA

    更新日期:1990-07-01 00:00:00

  • Kaposi's sarcoma-associated herpesvirus-encoded LANA interacts with host KAP1 to facilitate establishment of viral latency.

    abstract:UNLABELLED:Kaposi's sarcoma-associated herpesvirus (KSHV) typically displays two different phases in its life cycle, the default latent phase and the lytic phase. There is a short period of lytic gene expression in the early stage of KSHV primary infection. The factors involved in the shutdown process of lytic gene exp...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Sun R,Liang D,Gao Y,Lan K

    更新日期:2014-07-01 00:00:00

  • Widespread endogenization of densoviruses and parvoviruses in animal and human genomes.

    abstract::Parvoviruses infect humans and a broad range of animals, from mammals to crustaceans, and generally are associated with a variety of acute and chronic diseases. However, many others cause persistent infections and are not known to be associated with any disease. Viral persistence is likely related to the ability to in...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Liu H,Fu Y,Xie J,Cheng J,Ghabrial SA,Li G,Peng Y,Yi X,Jiang D

    更新日期:2011-10-01 00:00:00

  • CD4+ CD25+ T cells regulate vaccine-generated primary and memory CD8+ T-cell responses against herpes simplex virus type 1.

    abstract::It has become evident that naturally occurring CD25(+) regulatory T cells (T(reg) cells) not only influence self-antigen specific immune response but also dampen foreign antigen specific immunity. This report extends our previous findings by demonstrating that immunity to certain herpes simplex virus (HSV) vaccines is...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Toka FN,Suvas S,Rouse BT

    更新日期:2004-12-01 00:00:00

  • Coxsackievirus B4 infection of human fetal thymus cells.

    abstract::The infection of human fetal thymus organ cultures (FTOC) with coxsackievirus B4 E2 (CVB4 E2) was investigated. Both positive- and negative-strand viral RNA were detected by real-time quantitative reverse transcription-PCR (RT-PCR) in CVB4 E2-infected FTOC, which supported high yields of virus production (approximatel...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Brilot F,Geenen V,Hober D,Stoddart CA

    更新日期:2004-09-01 00:00:00

  • Fusion deficiency induced by mutations at the dimer interface in the Newcastle disease virus hemagglutinin-neuraminidase is due to a temperature-dependent defect in receptor binding.

    abstract::The tetrameric paramyxovirus hemagglutinin-neuraminidase (HN) protein mediates attachment to sialic acid-containing receptors as well as cleavage of the same moiety via its neuraminidase (NA) activity. The X-ray crystallographic structure of an HN dimer from Newcastle disease virus (NDV) suggests that a single site in...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Corey EA,Mirza AM,Levandowsky E,Iorio RM

    更新日期:2003-06-01 00:00:00

  • Genetic and functional analysis of R5X4 human immunodeficiency virus type 1 envelope glycoproteins derived from two individuals homozygous for the CCR5delta32 allele.

    abstract::We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR5delta32 homozygotes. Envs from both subjects used CCR5 and CXCR4 for entry into transfected cells. Most R5X4 Envs were lymphocyte-tropic and used CXCR4 exclusively for entry into peripheral bl...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Gray L,Churchill MJ,Keane N,Sterjovski J,Ellett AM,Purcell DF,Poumbourios P,Kol C,Wang B,Saksena NK,Wesselingh SL,Price P,French M,Gabuzda D,Gorry PR

    更新日期:2006-04-01 00:00:00

  • Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC.

    abstract::As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. N...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kibler KV,Asbach B,Perdiguero B,García-Arriaza J,Yates NL,Parks R,Stanfield-Oakley S,Ferrari G,Montefiori DC,Tomaras GD,Roederer M,Foulds KE,Forthal DN,Seaman MS,Self S,Gottardo R,Phogat S,Tartaglia J,Barnett S,Cris

    更新日期:2019-01-17 00:00:00

  • Activation of cytomegalovirus in pig-to-primate organ xenotransplantation.

    abstract::Xenotransplantation of porcine organs carries the risk of reactivation of latent virus in donor and recipient tissues as well as transmission of viruses between species. We have investigated the activation of baboon cytomegalovirus (BCMV) and porcine CMV (PCMV) in a pig-to-primate model of xenotransplantation. Tissues...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Mueller NJ,Barth RN,Yamamoto S,Kitamura H,Patience C,Yamada K,Cooper DK,Sachs DH,Kaur A,Fishman JA

    更新日期:2002-05-01 00:00:00

  • Influence of the rate of cell growth and cell density on interferon action in chick embryo cells.

    abstract::Chick embryo cells became more sensitive to the action of interferon the longer they remained in culture. This phenomenon was found even before confluency had been reached. The relative insensitivity of newly seeded cells was not due to a loss of receptors. Cells synthesizing deoxyribonucleic acid (DNA) at a high rate...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Rossman TG,Vilcek J

    更新日期:1969-07-01 00:00:00

  • Genetic Analysis of a Baculovirus, Autographa californica Nuclear Polyhedrosis Virus I. Isolation of Temperature-Sensitive Mutants and Assortment into Complementation Groups.

    abstract::Temperature-sensitive (ts) mutants were isolated from the baculovirus Autographa californica (alfalfa looper) MNPV, grown in Spodoptera frugiperda (fall armyworm) cells in the presence of N-methyl-N'-nitro-N-nitrosoguanidine. Of 567 plaque isolates screened, 27 were temperature sensitive (ts), representing a mutation ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Brown M,Crawford AM,Faulkner P

    更新日期:1979-07-01 00:00:00

  • Monocyte-derived cultured dendritic cells are susceptible to human immunodeficiency virus infection and transmit virus to resting T cells in the process of nominal antigen presentation.

    abstract::The susceptibility of monocyte-derived cultured dendritic cells (DCs) to human immunodeficiency virus (HIV) infection and their role in viral transmission in the immune response were studied in detail. We observed that highly purified cultured DCs were infected with the T-tropic Lai strain of HIV type 1 (HIV-1Lai) via...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Tsunetsugu-Yokota Y,Akagawa K,Kimoto H,Suzuki K,Iwasaki M,Yasuda S,Häusser G,Hultgren C,Meyerhans A,Takemori T

    更新日期:1995-07-01 00:00:00

  • Functional properties and genetic relatedness of the fusion and hemagglutinin-neuraminidase proteins of a mumps virus-like bat virus.

    abstract:UNLABELLED:A bat virus with high phylogenetic relatedness to human mumps virus (MuV) was identified recently at the nucleic acid level. We analyzed the functional activities of the hemagglutinin-neuraminidase (HN) and the fusion (F) proteins of the bat virus (batMuV) and compared them to the respective proteins of a hu...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Krüger N,Hoffmann M,Drexler JF,Müller MA,Corman VM,Sauder C,Rubin S,He B,Örvell C,Drosten C,Herrler G

    更新日期:2015-04-01 00:00:00

  • The K-bZIP protein from Kaposi's sarcoma-associated herpesvirus interacts with p53 and represses its transcriptional activity.

    abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been implicated in the pathogenesis of Kaposi's sarcoma. KSHV encodes K-bZIP (open reading frame K8), a protein that belongs to the basic region-leucine zipper (bZIP) family of transcription factors. Here we show that K-bZIP associates with ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Park J,Seo T,Hwang S,Lee D,Gwack Y,Choe J

    更新日期:2000-12-01 00:00:00

  • Coronavirus proteins: structure and function of the oligosaccharides of the avian infectious bronchitis virus glycoproteins.

    abstract::The recent finding that the E1 glycoproteins of murine coronaviruses contain only O-linked oligosaccharides suggested that this unusual modification might be a distinguishing feature of coronaviruses and might play an essential role in the life cycle of this family of viruses. To examine these possibilities, we analyz...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Stern DF,Sefton BM

    更新日期:1982-12-01 00:00:00

  • Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins.

    abstract::Coronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. The spike (S) homotrimers bind to their receptors via the receptor-binding domain (RB...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Shi Y,Shi J,Sun L,Tan Y,Wang G,Guo F,Hu G,Fu Y,Fu ZF,Xiao S,Peng G

    更新日期:2021-01-07 00:00:00

  • Full genomic sequence of the prototype strain (M64) of Rio Bravo virus.

    abstract::Rio Bravo virus (RBV) is a member of the family Flaviviridae, genus Flavivirus. It belongs to a group of viruses in the genus with no known vector. In this report, we analyze the complete genome of the prototype RBV, strain M64. ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Volkova E,Tesh RB,Monath TP,Vasilakis N

    更新日期:2012-04-01 00:00:00

  • A single mutation in the glycophorin A binding site of hepatitis A virus enhances virus clearance from the blood and results in a lower fitness variant.

    abstract::Hepatitis A virus (HAV) has previously been reported to bind to human red blood cells through interaction with glycophorin A. Residue K221 of VP1 and the surrounding VP3 residues are involved in such an interaction. This capsid region is specifically recognized by the monoclonal antibody H7C27. A monoclonal antibody-r...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Costafreda MI,Ribes E,Franch A,Bosch A,Pintó RM

    更新日期:2012-08-01 00:00:00

  • The ocr+ gene function of bacteriophages T3 and T7 counteracts the Salmonella typhimurium DNA restriction systems SA and SB.

    abstract::In host cells containing the Salmonella typhimurium DNA restriction-modification systems SA(+) and SB(+), replication of the ocr(+) bacteriophages T3 and T7 is not impaired. However, ocr (gene 0.3) mutants of these phages are susceptible to DNA restriction and modification by the SA(+) and SB(+) systems. ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Krüger DH,Hansen S,Reuter M

    更新日期:1983-03-01 00:00:00

  • DNA polymerase associated with human hepatitis B antigen.

    abstract::DNA polymerase activity was detected in each of eight preparations of concentrated human hepatitis B antigen (HBAg) rich in Dane particles prepared by high-speed centrifugation of antigen-positive human plasma and in none of seven control preparations prepared in the same way from HBAg-negative plasma. The incorporati...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kaplan PM,Greenman RL,Gerin JL,Purcell RH,Robinson WS

    更新日期:1973-11-01 00:00:00

  • Redox regulation of adenovirus-induced AP-1 activation by overexpression of manganese-containing superoxide dismutase.

    abstract::Adenovirus gene therapy is a promising tool in the clinical treatment of many genetic and acquired diseases. However, it has also caused pathogenic effects in organs such as the liver. The redox-sensitive transcription factors AP-1 and NF-kappaB have been implicated in these effects. To study the mechanisms of adenovi...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Zhang HJ,Drake VJ,Xu L,Hu J,Domann FE,Oberley LW,Kregel KC

    更新日期:2002-01-01 00:00:00

  • Computationally Optimized Broadly Reactive Hemagglutinin Elicits Hemagglutination Inhibition Antibodies against a Panel of H3N2 Influenza Virus Cocirculating Variants.

    abstract::Each influenza season, a set of wild-type viruses, representing one H1N1, one H3N2, and one to two influenza B isolates, are selected for inclusion in the annual seasonal influenza vaccine. In order to develop broadly reactive subtype-specific influenza vaccines, a methodology called computationally optimized broadly ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Wong TM,Allen JD,Bebin-Blackwell AG,Carter DM,Alefantis T,DiNapoli J,Kleanthous H,Ross TM

    更新日期:2017-11-30 00:00:00

  • RNA polymerase II is aberrantly phosphorylated and localized to viral replication compartments following herpes simplex virus infection.

    abstract::During lytic infection, herpes simplex virus subverts the host cell RNA polymerase II transcription machinery to efficiently express its own genome while repressing the expression of most cellular genes. The mechanism by which RNA polymerase II is directed to the viral delayed-early and late genes is still unresolved....

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Rice SA,Long MC,Lam V,Spencer CA

    更新日期:1994-02-01 00:00:00

  • Control of corynebacteriophage reproduction by heteroimmune repression.

    abstract::Corynebacteriophages beta and gamma are closely related but heteroimmune; hence, gamma reproduces in C7(beta). A series of gamma mutants, designated gamma-bin (beta-inhibited), has been isolated. They reproduce in only 2 to 14% of infected C7(beta) cells, and, as a result, plaque with an efficiency of 10(-4) to 10(-5)...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Groman N,Rabin M

    更新日期:1978-10-01 00:00:00

  • Elevated chemokine responses are maintained in lungs after clearance of viral infection.

    abstract::We observed two patterns of chemokine expression in the lungs of mice infected with murine gammaherpesvirus 68: peaks of chemokine expression correlated with or occurred after the peak of viral gene expression. Chemokine expression remained elevated through 29 days postinfection. ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Weinberg JB,Lutzke ML,Efstathiou S,Kunkel SL,Rochford R

    更新日期:2002-10-01 00:00:00

  • P108 and T109 on E2 Glycoprotein Domain I Are Critical for the Adaptation of Classical Swine Fever Virus to Rabbits but Not for Virulence in Pigs.

    abstract::The classical swine fever virus (CSFV) live attenuated vaccine C-strain is adaptive to rabbits and attenuated in pigs, in contrast with the highly virulent CSFV Shimen strain. Previously, we demonstrated that P108 and T109 on the E2 glycoprotein (E2P108-T109) in domain I (E2DomainI) rather than R132, S133, and D191 in...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Xie L,Han Y,Ma Y,Yuan M,Li W,Li LF,Li M,Sun Y,Luo Y,Li S,Hu S,Li Y,Qiu HJ

    更新日期:2020-08-17 00:00:00

  • Antigenic characterization of type C RNA virus isolates of gibbon apes.

    abstract::Type C RNA viruses initially isolated from a lymphosarcoma of a gibbon ape and from a fibrosarcoma of a woolly monkey are very closely related immunologically. However, recent studies have shown that these viruses are distinguishable in a radioimmunoassay for the 12,000-molecular-weight polypeptide (p12) of the woolly...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Tronick SR,Stephenson JR,Aaronson SA,Kawakami TG

    更新日期:1975-01-01 00:00:00

  • Glycoproteins of measles virus under reducing and nonreducing conditions.

    abstract::Measles virus has two glycoproteins. The larger glycoprotein (HA) is composed of 76,000-dalton subunits that are bound by disulfide bonds. The smaller glycoprotein (F) appears to contain a glucosamine-rich portion that is linked to an unglycosylated protein by disulfide bonds. ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Hardwick JM,Bussell RH

    更新日期:1978-02-01 00:00:00