The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase.


:It is not yet clear to what extent depletion of intracellular GTP pools contributes to the antiviral activity of ribavirin. Therefore, the antiviral activities of (i) ribavirin, (ii) its 5-ethynyl analogue, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), and (iii) mycophenolic acid (MPA) (a compound that inhibits only cellular IMP dehydrogenase activity) were studied on the replication of flaviviruses and paramyxoviruses. In addition, the effects of these three compounds on intracellular GTP pools were assessed. A linear correlation was observed over a broad concentration range between the antiviral activities of ribavirin, EICAR, and MPA and the effects of these compounds on GTP pool depletion. When the 50% effective concentrations (EC50s) for the antiviral activities of ribavirin, EICAR, and MPA were plotted against the respective EC50 values for GTP pool depletion, a linear correlation was calculated. These data provide compelling evidence that the predominant mechanism of action of ribavirin in vitro against flavi- and paramyxoviruses is based on inhibition of cellular IMP dehydrogenase activity.


J Virol


Journal of virology


Leyssen P,Balzarini J,De Clercq E,Neyts J




Has Abstract


2005-02-01 00:00:00














  • Electron microscopy of simian virus 40 DNA configuration under denaturation conditions.

    abstract::After isolation, the DNA of simian virus 40 appeared as a negative supertwist (form I) or as an open circle with at least one single-strand scission (form II). Under the denaturation conditions usually applied, such as heating in the presence of formaldehyde or application of alkali, form I molecules could appear as "...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Mayer F,Mazaitis AJ,Pühler A

    更新日期:1975-03-01 00:00:00

  • Mutational analysis of open reading frame E4 of bovine papillomavirus type 1.

    abstract::Open reading frame (ORF) E4 is a 353-base-pair ORF of bovine papillomavirus type 1. To determine the biological activities of this ORF in mouse C127 cells, we analyzed the effects of two constructed mutations which are predicted to prevent synthesis of ORF E4 proteins while leaving the amino acid sequence encoded by t...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Neary K,Horwitz BH,DiMaio D

    更新日期:1987-04-01 00:00:00

  • Degradation of cellular mRNAs induced by a virion-associated factor during herpes simplex virus infection of Vero cells.

    abstract::We have used Northern blot hybridization to study the accumulation of specific cellular mRNAs in Vero cells infected with herpes simplex virus (HSV) type 1 or type 2. HSV-1 infection decreased the cytoplasmic levels of beta- and gamma-actin, beta-tubulin, and histone H3 and H4 mRNAs, though not all at the same rate. H...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Schek N,Bachenheimer SL

    更新日期:1985-09-01 00:00:00

  • Differential effects of human cytomegalovirus on integrated and unintegrated human immunodeficiency virus sequences.

    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


    authors: Koval V,Jault FM,Pal PG,Moreno TN,Aiken C,Trono D,Spector SA,Spector DH

    更新日期:1995-03-01 00:00:00

  • Complete genome sequence of a Newcastle disease virus strain isolated from broiler breeder flocks in China.

    abstract::In 2010 and 2011, several devastating Newcastle disease (ND) outbreaks occurred in China, affecting broilers, layers, and breeders. The CK-JSX1-201005 virus was isolated from broiler breeder flocks vaccinated with the classical ND virus (NDV) vaccine program, but laying rate decreased from 80% to 30 to 40% in the clin...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Chen F,Liu J,Liu D,Yan Z,Ji J,Qin J,Li H,Ma J,Bi Y,Xie Q

    更新日期:2012-11-01 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

  • Andes virus recognition of human and Syrian hamster beta3 integrins is determined by an L33P substitution in the PSI domain.

    abstract::Andes virus (ANDV) causes a fatal hantavirus pulmonary syndrome (HPS) in humans and Syrian hamsters. Human alpha(v)beta(3) integrins are receptors for several pathogenic hantaviruses, and the function of alpha(v)beta(3) integrins on endothelial cells suggests a role for alpha(v)beta(3) in hantavirus directed vascular ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Matthys VS,Gorbunova EE,Gavrilovskaya IN,Mackow ER

    更新日期:2010-01-01 00:00:00

  • Effective vaccination against long-term gammaherpesvirus latency.

    abstract::The fundamental question of whether a primed immune system is capable of preventing latent gammaherpesvirus infection remains unanswered. Recent studies showing that vaccination can reduce acute replication and short-term latency but cannot alter long-term latency further call into question the possibility of achievin...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Tibbetts SA,McClellan JS,Gangappa S,Speck SH,Virgin HW 4th

    更新日期:2003-02-01 00:00:00

  • Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection.

    abstract::We characterized the cellular immune response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in 12- to 14-month-old BALB/c mice, a model that mimics features of the human disease. Following intranasal administration, the virus replicated in the lungs, with peak titers on day 2 postinfection. Enh...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Chen J,Lau YF,Lamirande EW,Paddock CD,Bartlett JH,Zaki SR,Subbarao K

    更新日期:2010-02-01 00:00:00

  • Specificities of monoclonal and polyclonal antibodies that inhibit adsorption of herpes simplex virus to cells and lack of inhibition by potent neutralizing antibodies.

    abstract::Polyclonal and monoclonal antibodies to individual herpes simplex virus (HSV) glycoproteins were tested for ability to inhibit adsorption of radiolabeled HSV type 1 (HSV-1) strain HFEMsyn [HSV-1(HFEM)syn] to HEp-2 cell monolayers. Polyclonal rabbit antibodies specific for glycoprotein D (gD) or gC and three monoclonal...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Fuller AO,Spear PG

    更新日期:1985-08-01 00:00:00

  • Pandemic H1N1 2009 influenza A virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons.

    abstract::In less than 3 months after the first cases of swine origin 2009 influenza A (H1N1) virus infections were reported from Mexico, WHO declared a pandemic. The pandemic virus is antigenically distinct from seasonal influenza viruses, and the majority of human population lacks immunity against this virus. We have studied ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Osterlund P,Pirhonen J,Ikonen N,Rönkkö E,Strengell M,Mäkelä SM,Broman M,Hamming OJ,Hartmann R,Ziegler T,Julkunen I

    更新日期:2010-02-01 00:00:00

  • Impact of quaternary organization on the antigenic structure of the tick-borne encephalitis virus envelope glycoprotein E.

    abstract::The envelope protein E of flaviviruses mediates both receptor-binding and membrane fusion. At the virion surface, 180 copies of E are tightly packed and organized in a herringbone-like icosahedral structure, whereas in noninfectious subviral particles, 60 copies are arranged in a T=1 icosahedral symmetry. In both case...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kiermayr S,Stiasny K,Heinz FX

    更新日期:2009-09-01 00:00:00

  • Modest truncation of the major capsid protein abrogates B19 parvovirus capsid formation.

    abstract::In vitro studies have suggested an important role for the minor capsid protein (VP1) unique region and the junction between VP1 and the major capsid protein (VP2) in the neutralizing immune response to B19 parvovirus. We investigated the role of the NH2-terminal region of the major structural protein in capsid structu...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kawase M,Momoeda M,Young NS,Kajigaya S

    更新日期:1995-10-01 00:00:00

  • Genetic location of a mutant of bacteriophage T4 deficient in the ability to induce endonuclease II.

    abstract::Reciprocal three-factor crosses and the use of a partial revertant of a putative ribonucleotide reductase mutant of Escherichia coli B/5 as indicator have made it possible to map denA (deficient in endonuclease II) between nrd-11 (ribonucleotide reductase gene B) and amM69 (gene 63) on the bacteriophage T4 chromosome....

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Ray P,Sinha NK,Warner HR,Snustad DP

    更新日期:1972-01-01 00:00:00

  • Comparison of an avian osteopetrosis virus with an avian lymphomatosis virus by RNA-DNA hybridization.

    abstract::Myeloblastosis-associated virus (MAV)-2(0), a virus which was derived from avian myeloblastosis virus and induced a high incidence of osteopetrosis, was compared with avian lymphomatosis virus 5938, a recent field isolate which induced a high incidence of lymphomatosis. The following information was obtained. (i) MAV-...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Smith RE,Davids LJ,Neiman PE

    更新日期:1975-01-01 00:00:00

  • Complete genome sequence of Klebsiella pneumoniae phage JD001.

    abstract::Klebsiella pneumoniae is a member of the family Enterobacteriaceae, opportunistic pathogens that are among the eight most prevalent infectious agents in hospitals. The emergence of multidrug-resistant strains of K. pneumoniae has became a public health problem globally. To develop an effective antimicrobial agent, we ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Cui Z,Shen W,Wang Z,Zhang H,Me R,Wang Y,Zeng L,Zhu Y,Qin J,He P,Guo X

    更新日期:2012-12-01 00:00:00

  • Interleukin-12 (IL-12), but not IL-23, deficiency ameliorates viral encephalitis without affecting viral control.

    abstract::The relative contributions of interleukin-12 (IL-12) and IL-23 to viral pathogenesis have not been extensively studied. IL-12p40 mRNA rapidly increases after neurotropic coronavirus infection. Infection of mice defective in both IL-12 and IL-23 (p40(-/-)), in IL-12 alone (p35(-/-)), and in IL-23 alone (p19(-/-)) revea...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kapil P,Atkinson R,Ramakrishna C,Cua DJ,Bergmann CC,Stohlman SA

    更新日期:2009-06-01 00:00:00

  • Requirements for lymphocyte activation by unusual strains of simian immunodeficiency virus.

    abstract::When residues 17 and 18 in nef of simian immunodeficiency virus strain SIVmac239 were changed from RQ to YE, the resultant virus was able to replicate in peripheral blood mononuclear cell cultures without prior lymphocyte activation and without the addition of exogenous interleukin-2, caused extensive lymphocyte activ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Du Z,Ilyinskii PO,Sasseville VG,Newstein M,Lackner AA,Desrosiers RC

    更新日期:1996-06-01 00:00:00

  • Interferon Regulatory Factor 7 Attenuates Chronic Gammaherpesvirus Infection.

    abstract::Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections and are associated with a variety of malignancies, including lymphomas. Interferon regulatory factor 7 (IRF-7) is an innate immune transcription factor that restricts acute replication of diverse viruses, including murine gammaherpesvirus 6...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Johnson KE,Aurubin CA,Jondle CN,Lange PT,Tarakanova VL

    更新日期:2020-11-23 00:00:00

  • Virus attenuation and identification of structural proteins of vaccinia virus that are selectively modified during virus persistence.

    abstract::To investigate the genetic stability of vaccinia virus DNA, we have tested whether alterations occurred in the polypeptide composition of this complex virus during persistent infections. We found that variants isolated at various passages in Friend erythroleukemia cells persistently infected with vaccinia virus contai...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Paez E,Dallo S,Esteban M

    更新日期:1987-08-01 00:00:00

  • Mouse DNA primase plays the principal role in determination of permissiveness for polyomavirus DNA replication.

    abstract::We have investigated the species-specific replication of polyomavirus DNA in the cell-free system that was established previously (Y. Murakami, T. Eki, M. Yamada, C. Prives, and J. Hurwitz, Proc. Natl. Acad. Sci. USA 83:6347-6351, 1986). Extracts from various species of cells supported polyomavirus DNA replication in ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Eki T,Enomoto T,Masutani C,Miyajima A,Takada R,Murakami Y,Ohno T,Hanaoka F,Ui M

    更新日期:1991-09-01 00:00:00

  • Flow field-flow fractionation: new method for separating, purifying, and characterizing the diffusivity of viruses.

    abstract::The nature and theory of flow field-flow fractionation is described, and its potential applicability to virus-like particles is discussed. Different virus types are shown to be retained at different levels. Retention can be controlled by variation of the experimental parameters, in good agreement with theory. However,...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Giddings JC,Yang FJ,Myers MN

    更新日期:1977-01-01 00:00:00

  • CD4(+) T cells induced by a DNA vaccine: immunological consequences of epitope-specific lysosomal targeting.

    abstract::Our previous studies have shown that targeting DNA vaccine-encoded major histocompatibility complex class I epitopes to the proteasome enhanced CD8(+) T-cell induction and protection against lymphocytic choriomeningitis virus (LCMV) challenge. Here, we expand these studies to evaluate CD4(+) T-cell responses induced b...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Rodriguez F,Harkins S,Redwine JM,de Pereda JM,Whitton JL

    更新日期:2001-11-01 00:00:00

  • Interaction of poly(rC) binding protein 2 with the 5' noncoding region of hepatitis A virus RNA and its effects on translation.

    abstract::Utilization of internal ribosome entry segment (IRES) structures in the 5' noncoding region (5'NCR) of picornavirus RNAs for initiation of translation requires a number of host cell factors whose distribution may vary in different cells and whose requirement may vary for different picornaviruses. We have examined the ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Graff J,Cha J,Blyn LB,Ehrenfeld E

    更新日期:1998-12-01 00:00:00

  • Influence of complement on the neutralization of murine cytomegalovirus by rabbit antibody.

    abstract::Antiserum against murine cytomegalovirus produced in the rabbit contained complement (C')-requiring neutralizing (CRN) antibody. The proportion of CRN was extremely high (up to 98%) during the early portion of an immunization procedure, whereas the antisera produced late had a much lower proportion that required C'. T...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kim KS,Carp RI

    更新日期:1973-12-01 00:00:00

  • The 86-kilodalton IE-2 protein of human cytomegalovirus is a sequence-specific DNA-binding protein that interacts directly with the negative autoregulatory response element located near the cap site of the IE-1/2 enhancer-promoter.

    abstract::The 86-kDa IE-2 protein of human cytomegalovirus is able to autoregulate its own expression via a short nucleotide sequence, termed the cis repression signal (CRS), that is located between the TATA box and the cap site of the IE-1/2 enhancer-promoter. Here we report that the 86-kDa IE-2 protein can interact directly w...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Lang D,Stamminger T

    更新日期:1993-01-01 00:00:00

  • West Nile virus inhibits the signal transduction pathway of alpha interferon.

    abstract::West Nile virus (WNV) is a human pathogen that can cause neurological disorders, including meningoencephalitis. Experiments with mice and mammalian cell cultures revealed that WNV exhibited resistance to the innate immune program induced by alpha interferon (IFN-alpha). We have investigated the nature of this inhibiti...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Guo JT,Hayashi J,Seeger C

    更新日期:2005-02-01 00:00:00

  • Inhibition of host translation in encephalomyocarditis virus-infected L cells: a novel mechanism.

    abstract::Encephalomyocarditis virus induced a rapid shutoff of host translation in mouse L cells shortly after infection and before viral proteins were made in detectable amounts. This kinetic pattern is similar to that seen in poliovirus-infected HeLa cells. However, the mechanisms of host shutoff are different in these two c...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Jen G,Thach RE

    更新日期:1982-07-01 00:00:00

  • Propagation of prion strains through specific conformers of the prion protein.

    abstract::Two prion strains with identical incubation periods in mice exhibited distinct incubation periods and different neuropathological profiles upon serial transmission to transgenic mice expressing chimeric Syrian hamster/mouse (MH2M) prion protein (PrP) genes [Tg(MH2M) mice] and subsequent transmission to Syrian hamsters...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Scott MR,Groth D,Tatzelt J,Torchia M,Tremblay P,DeArmond SJ,Prusiner SB

    更新日期:1997-12-01 00:00:00

  • Identification, characterization, and sequence analysis of a cDNA encoding a phosphoprotein of human herpesvirus 6.

    abstract::Human herpesvirus 6 (HHV-6)-specific monoclonal antibody (Mab) 9A5D12 reacted with the nucleus of HHV-6 strain GS-infected cells and immunoprecipitated a phosphorylated polypeptide with an approximate size of 41 kDa, designated HHV-6 P41. A 110-kDa polypeptide was also immunoprecipitated by the MAb. These polypeptides...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Chang CK,Balachandran N

    更新日期:1991-06-01 00:00:00