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At least 1,243 records · Page 69Linked to original sources
PubMed2003

Replacement of murine leukemia virus readthrough mechanism by human immunodeficiency virus frameshift allows synthesis of viral proteins and virus replication.

Retroviruses use unusual recoding strategies to synthesize the Gag-Pol polyprotein precursor of viral enzymes. In human immunodeficiency virus, ribosomes translating full-length viral RNA can shift back by 1 nucleotide at a specific site defined by the presence of both a slippery sequence and a downstream stimulatory element made of an extensive secondary structure. This so-called frameshift mechanism could become a target for the development of novel antiviral strategies. A different recoding strategy is used by other retroviruses, such as murine leukemia viruses, to synthesize the Gag-Pol precursor; in this case, a stop codon is suppressed in a readthrough process, again due to the presence of a specific structure adopted by the mRNA. Development of antiframeshift agents will greatly benefit from the availability of a simple animal and virus model. For this purpose, the murine leukemia virus readthrough region was rendered inactive by mutagenesis and the frameshift region of human immunodeficiency virus was inserted to generate a chimeric provirus. This substitution of readthrough by frameshift allows the synthesis of viral proteins, and the chimeric provirus sequence was found to generate infectious viruses. This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model.

3T3 Cells↗
PubMed1977

[Study of the morphological aspects of Okhotskiĭ virus replication in a chick fibroblast culture].

Electron microscopic studies of chick embryo fibroblast cells 24 hours after infection with Okhotsky virus revealed changes typical orbivirus infection in the cytoplasm and the nuclei of the cells. The nuclei of the infected cells contained fine-granular matrices with forming virus particles and tubular structures. The cell cytoplasm also contained tubular structures, crystal arrays, fine-granular matrices and virus particles 50-60 nm in diameter.

Animals↗
PubMed1999

Detection of hepatitis-C virus and hepatitis-C virus replication in hepatocellular carcinoma by in situ hybridization.

BACKGROUND: Although hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma (HCC), the role of this virus in carcinogenesis is not fully understood. METHODS: We studied HCV infection and replication by detecting plus- and minus-strand HCV RNA by in situ hybridization (ISH) in surgically resected HCCs and adjacent non-cancerous tissue obtained from 15 anti-HCV antibody-positive patients with HCC. RESULTS: Plus-strand HCV RNA was found in 9 of 15 HCCs. Both plus- and minus-strand HCV RNA were detected in four of these nine patients. In non-cancerous tissues obtained adjacent to the HCC, plus-strand HCV RNA was found in 10 of 15 patients, whereas both plus- and minus-strand HCV RNA were detected in 7 of these 10 patients. The degree of staining by ISH did not correlate with the differentiation of the HCC, histologic classification of the non-cancerous tissue, serum HCV RNA levels, or serum transaminase levels. CONCLUSIONS: HCV can be found in and replicates in both hepatoma cells and in non-cancerous hepatocytes in anti-HCV antibody-positive patients with HCC. The direct effects of HCV viral gene products on normal hepatocytes in the development of HCC require additional study.

Aged↗
PubMed2002

Woodchuck gamma interferon upregulates major histocompatibility complex class I transcription but is unable to deplete woodchuck hepatitis virus replication intermediates and RNAs in persistently infected woodchuck primary hepatocytes.

Gamma interferon (IFN-gamma) is an important mediator with multiple functions in the host defense against viral infection. IFN-gamma, in concert with tumor necrosis factor alpha (TNF-alpha), leads to a remarkable reduction of intrahepatic replication intermediates and specific mRNAs of hepatitis B virus (HBV) by a noncytolytic mechanism in the transgenic mouse model. Thus, it is rational to evaluate the potential value of IFN-gamma for the treatment of chronic HBV infection. In the present study, we expressed recombinant woodchuck IFN-gamma (wIFN-gamma) in Escherichia coli and mammalian cells. wIFN-gamma protected woodchuck cells against infection of murine encephalomyocarditis virus in a species-specific manner. It upregulated the mRNA level of the woodchuck major histocompatibility complex class I (MHC-I) heavy chain in permanent woodchuck WH12/6 cells and regulated differentially the gene expression. However, the level of the replication intermediates and specific RNAs of woodchuck hepatitis virus (WHV) in persistently WHV-infected primary woodchuck hepatocytes did not change despite a treatment with 1,000 U of wIFN-gamma per ml or with a combination of wIFN-gamma and woodchuck TNF-alpha. Rather, hepatocytes derived from chronic carriers had an elevated level of the MHC-I heavy-chain mRNAs, most probably due to the exposure to inflammatory cytokines in vivo. Treatment with high doses of wIFN-gamma led to an abnormal cell morphology and loss of hepatocytes. Thus, wIFN-gamma regulates the gene expression in woodchuck hepatocytes but could not deplete WHV replication intermediates and mRNAs in persistently infected hepatocytes. The cellular response to wIFN-gamma may be changed in hepatocytes from chronically WHV-infected woodchucks. It should be clarified in the future whether the continuous exposure of hepatocytes to inflammatory cytokines or the presence of viral proteins leads to changes of the cellular response to wIFN-gamma.

Animals↗
PubMed1992

Proteolysis is a key process in virus replication.

Proteases were amongst the first enzymes to be isolated and crystallized, and the discovery of their existence in viruses and the realization of the vital role they play has given a new lease of life to one of the oldest topics in biochemistry. Already we have seen the discovery of new variations on well-studied reaction mechanisms and there is the promise of others to come that may be totally novel. When this is allied to the prospect of developing the knowledge which is beginning to accrue into a much needed antiviral therapy, it is clear that viral proteases and their key role in viral replication will be an increasing focus of attention for some time to come.

Animals↗
PubMed1995

Effects of Aspergillus terreus extract on herpes simplex 1 virus replication.

In this study we reported about the antiviral activity of Aspergillus terreus alcohol extract against Herpes simplex type 1 virus. This activity is dose-dependent, is related to the concentration of the challenging virus and depends particularly on a proteic fraction of 5-10 Kda. Optimal effects were observed with doses ranging from 25 to 6.25 micrograms/ml for crude alcohol extract and up to 3 micrograms/ml for 5-10 Kda fraction. Moreover, antiviral activity was evident in viral replication, but not on virus out of the cells. An increased 3H thymidine incorporation was noted on infected cells treated with the extract and this effect may suggest an intracellular accumulation of viral DNA in the absence or reduction of virion production.

Antiviral Agents↗
PubMed1980

Acyclovir inhibition of Epstein-Barr virus replication.

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] triphosphate inhibits Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase; EC 2.7.7.7) to a greater extent than it inhibits host alpha and beta DNA polymerases. The affinity of the compound for viral polymerase is 100-fold higher than for alpha-polymerase. The extent of inhibition is dependent upon the base composition of the template-primer. The inhibition is prevented by increasing concentrations of deoxyguanosine triphosphate. The EBV-associated DNA polymerase reaction in the presence of the inhibitor, although depressed, proceeds at a linear rate over a long period of time. In contrast, the reaction of Escherichia coli DNA polymerase I in the presence of 2',3'-dideoxythymidine 5'-triphosphate, a DNA chain terminator, levels off after initial linearity. Preincubation of acyclovir triphosphate with DNA and enzyme does not increase its inhibitory activity. The virus-producing cell line P3HRF-1 consistently shows reduced viral genome numbers and viral capsid antigen on prolonged exposure to acyclovir. The number of EBV genomes returns to the control level when the cells are grown in drug-free medium. The results suggest that a competitive mechanism is the major mode of acyclovir inhibition of EBV replication.

Acyclovir↗
PubMed1997

Inhibition of Japanese encephalitis virus infection by nitric oxide: antiviral effect of nitric oxide on RNA virus replication.

The antiviral effects of nitric oxide (NO) on Japanese encephalitis virus (JEV), a member of the family Flaviviridae, were investigated in this study. In vitro, inhibition of replication of JEV in gamma interferon-activated RAW 264.7 murine macrophages was correlated to cellular NO production. When cocultured with infected murine neuroblastoma N18 cells, gamma interferon-activated RAW 264.7 cells also efficiently hindered JEV replication in contiguous bystanders, and this anti-JEV effect could be reversed by an NO synthase (NOS) inhibitor, N-monomethyl-L-arginine acetate. In vivo, the mortality rate increased as the NOS activity of JEV-infected mice was inhibited by its competitive inhibitor, N-nitro-L-arginine methyl ester. Moreover, when an organic donor, S-nitro-N-acetylpenicillamine (SNAP), was used, the NO-mediated antiviral effect was also observed in primarily JEV-infected N18, human neuronal NT-2, and BHK-21 cells, as well as in persistently JEV-infected C2-2 cells. These data reaffirm that NO has an effective and broad-spectrum antimicrobial activity against diversified intracellular pathogens. Interestingly, the antiviral effect of NO was not enhanced by treatment of N18 cells with SNAP prior to JEV infection, a measure which has been shown to greatly increase the antiviral effect of NO in infection by vesicular stomatitis virus. From biochemical analysis of the impact of NO on JEV replication in cell culture, NO was found to profoundly inhibit viral RNA synthesis, viral protein accumulation, and virus release from infected cells. The results herein thus suggest that NO may play a crucial role in the innate immunity of the host to restrict the initial stage of JEV infection in the central nervous system.

Animals↗
PubMed1991

Fc receptors do not mediate African swine fever virus replication in macrophages.

Titration experiments in swine macrophages have shown that African swine fever virus infectivity was not enhanced in the presence of antiviral antibodies. The early viral protein synthesis and the viral DNA replication in swine macrophages infected with virus-antibody complexes were inhibited in the presence of high doses of uv-inactivated virus, which saturated specific virus receptors, but not when Fc receptors were saturated with antibodies. These results indicate that African swine fever virus does not infect swine macrophages through Fc receptors and that the normal entry pathway through virus receptors is not bypassed by the virus-antibody complexes.

African Swine Fever Virus↗
PubMed1986

In vivo effects of coronavirus-specific T cell clones: DTH inducer cells prevent a lethal infection but do not inhibit virus replication.

A lethal infection by neurotropic JHM strain of mouse hepatitis virus was prevented by the local adoptive transfer of three virus-specific Lyt-1+2-, L3T4+ T cell clones. The transfer of Lyt-1+ T cells specific for an unrelated antigen (hen egg lysozyme) did not protect. Protection required I region compatibility between the T cells and the recipients, and was reversed either by irradiation of the cells before transfer or by pretreatment of the recipients with cyclophosphamide. Adoptive transfer prevented death due to JHM virus infection but did not result in altered antiviral immunoglobulin synthesis or the suppression of viral replication in the central nervous system (CNS). The data presented implicate a local DTH response in the protection of the host from lethal infection of the CNS by a neurotropic virus, but clearly imply that other antiviral effector mechanisms are necessary for the suppression of viral replication.

Animals↗
PubMed2005

Alcohol has no effect on hepatitis C virus replication: a meta-analysis.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection who consume large quantities of alcohol have more severe liver disease compared with HCV patients without a history of alcohol consumption. The mechanism by which alcohol worsens HCV related liver disease is not properly understood. One possibility is that alcohol stimulates HCV replication, and the present meta-analysis was performed to examine this issue. METHODS: The effect of alcohol on viral titres was assessed in three ways: comparison of the heaviest drinkers with non-drinkers; effect of graded doses of alcohol; and effect of abstinence in the same individual. RESULTS: A total of 14 studies were identified. Comparison of patients with the highest alcohol use with the abstinent group showed a significant association with viral load in three studies, five studies had a positive direction, while the remaining four studies found a negative relationship. Analysis of the combined results showed no association between alcohol consumption and virus levels (p = 0.29). Assessment of graded doses of alcohol also showed no significant difference between non-drinkers and moderate drinkers (p = 0.50), between non-drinkers and heavy drinkers (p = 0.35), or between moderate drinkers and heavy drinkers (p = 0.32). Five studies examined the influence of abstinence on viral titres but none provided sufficient data for statistical analysis. CONCLUSIONS: The present study has failed to show an association between alcohol use and HCV viral titres. These observations raise the possibility that the hepatic damage caused by alcohol and HCV may be purely additive, involving different mechanisms and pathways.

Alcohol Drinking↗
PubMed1990

Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells.

We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions.

Antiviral Agents↗
PubMed1990

Synergistic inhibition of human immunodeficiency virus replication in vitro by combinations of 3'-azido-3'-deoxythymidine and 3'-fluoro-3'-deoxythymidine.

The antiviral activity against human immunodeficiency virus type 1 of the two structurally related thymidine analogs azidothymidine and fluorothymidine, both alone and in combination, was tested. Fluorothymidine was tenfold more active than azidothymidine. The selectivity indices of the two compounds were similar. The combination of azidothymidine and fluorothymidine showed clearly synergistic antiviral activity, and diminished cytotoxicity. The inhibition of reverse transcriptase from human immunodeficiency virus type 1 by the triphosphates of azidothymidine and fluorothymidine, both alone and in combination was also tested. Azidothymidine triphosphate was a fourfold stronger inhibitor than fluorothymidine triphosphate. The combination of the two showed only additive (and not synergistic) effects upon reverse transcriptase. The combination of azidothymidine and fluorothymidine showed both synergistic antiviral activity and diminished cytotoxicity, and may therefore represent a promising therapeutic strategy. The additive (and not synergistic) inhibition of reverse transcriptase by the combination of the triphosphates indicates that in cell culture additional factors other than inhibition of the reverse transcriptase by the triphosphates influence the antiviral activity of the combination. Such factors might include effects upon normal nucleoside metabolism or metabolism of the analogs. Alternatively, one of the nucleosides might have an additional mechanism of action besides inhibition of the reverse transcriptase.

Antiviral Agents↗
PubMed1975

Herpes simplex virus encephalitis in suckling mice: ultrastructural studies of virus replication.

Ultrastructural studies concerning the replication and release of a neuro-adapted strain of herpes simplex virus were carried out on acutely encephalitic mice. It was found that envelopment of nucleocapsid particles at the nuclear membrane of brain cells was inefficient, resulting in accumulation of unenveloped nucleocapsids in the cell cytoplasm. These nucleocapsids were associated with arrays of microtubules within cytoplasmic processes. Enveloped particles were rarely present in tissur spaces. Those that were seen appeared to be in a state of disintegration. This replication process of herpes simplex virus in the murine encephalitis model differs from that observed in tissue culture cells. The implications of these differences are discussed.

Animals↗