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At least 451 records · Page 25Linked to original sources
PubMed1994

Cyclosporin A inhibits vaccinia virus replication in vitro.

The effect of the immune modulator, Cyclosporin A (CsA) on vaccinia virus replication has been examined in cell cultures. In the present study we report that CsA is anti-viral towards vaccinia virus. Viral yield was inhibited by more than 97% after 24 h postinfection in the presence of 16 microM to 40 microM CsA. An analysis of the infectious cycle in greater detail revealed that CsA did not effect the total level of [35S] methionine incorporation into vaccinia infected cells. However, both early and late viral gene expression were inhibited by CsA. Late viral protein synthesis appeared to be more sensitive to the drug. At least one late viral polypeptide of approximately Mr 38,000 was virtually undetected up to 8 h postinfection in the presence of 40 microM CsA. Host protein synthesis which is normally inhibited by the virus was not turned off until very late in infection. Viral DNA replication was also inhibited by the addition of CsA at levels comparable to those observed for late protein synthesis.

Animals↗
PubMed2002

Coumarins and pyranocoumarins, potential novel pharmacophores for inhibition of measles virus replication.

A series of coumarin and pyranocoumarin analogues were evaluated in vitro for antiviral efficacy against measles virus (MV), strain Chicago. Of the 22 compounds tested for inhibition, six were found to have selectivity indices greater than 10. These were compounds 5-hydroxy-7-propionyloxy-4-propylcoumarin (2a), 5,7-bis(tosyloxy)-4-propylcoumarin (7); 5-hydroxy-4-propyl-7-tosyloxy-coumarin (8); 6,6-dimethyl-9-propionyloxy-4-propyl-2H,6H-benzo[1,2-b:3,4-b']dipyran-2-one (9); 6,6-dimethyl-9-pivaloyloxy-4-propyl-2H,6H-benzo[1,2-b:3,4-b']dipyran-2-one (10); and 7,8-cis-10,11,12-trans-4-propyl-6,6,10,11-tetramethyl-7,8,9-trihydroxy-2H,6H,12H-benzo[1 ,2-b:3,4-b':5,6-b'']tripyran-2-one (18). Three of the active drugs were propyl coumarin analogues (2a, 7 and 8), two were dipyranone or chromeno-coumarins (9 and 10), and one was a benzotripyranone with a coumarin nucleus (18). Some appeared to be rather specific and potent inhibitors of MV with EC50 values ranging from 0.2 to 50 microg/ml and the majority of the EC50 values being less than 5 pg/ml. The compounds inhibited an additional nine strains of MV, and in virucidal tests the drugs did not physically disrupt the virion to inhibit virus replication. The inhibitory activity for one of the compounds tested (7) was somewhat dependent on virus concentration and it was still active when added to cells up to 24 h after virus exposure. When used in combination with ribavirin, compound 7 appeared not to profoundly affect the antiviral efficacy of ribavirin or its cell-associated toxicity. However, a slightly antagonistic MV-inhibitory effect was observed at the highest concentration of ribavirin used in combination with most concentrations of compound 7 tested. This and related compounds may be valuable leads in the development of a potent and selective class of MV inhibitors that could be used in future in the clinic.

Animals↗
PubMed1996

Short report: lack of virus replication in arthropods after intrathoracic inoculation of Ebola Reston virus.

To evaluate the potential for arthropods to serve as reservoir hosts of Ebola virus, three mosquito species, Aedes albopictus, Aedes taeniorhynchus, and Culex pipiens, and a soft tick, Ornithodoros sonrai, were inoculated with 1O2.5 plaque-forming units of Ebola Reston virus. After incubation at 22 degrees C for 11 days, at least six specimens of each species were triturated and examined for evidence of viral replication by enzyme-linked immunosorbent assay and plaque assay. There was no evidence of viral replication in any of the arthropods tested. Because intrathoracic inoculation bypasses various barriers to viral infection, the lack of replication of Ebola Reston virus in these inoculated arthropods indicates that these mosquito species and soft ticks probably are not involved as natural reservoirs of Ebola virus.

Aedes↗
PubMed1991

Naturally occurring missense mutation in the polymerase gene terminating hepatitis B virus replication.

A hepatitis B virus (HBV) genome was cloned from human liver. Numerous mutations in all viral genes define this HBV DNA as a mutant, divergent from all known HBV DNA sequences. Functional analyses of this mutant demonstrated a defect blocking viral DNA synthesis. The genetic basis of this defect was identified as a single missense mutation in the 5' region of the viral polymerase gene, resulting in the inability to package pregenomic RNA into core particles. The replication defect could be trans-complemented by a full-length wild-type, but not by a full-length mutant or 3'-truncated wild-type, polymerase gene construct. Our findings indicate a critical role of the 5' polymerase gene region in the life cycle of the virus and suggest that introducing missense mutations in this region can be a strategy to terminate viral replication in vivo.

Base Sequence↗
PubMed1996

trans-Acting factors, detoxication enzymes and hepatitis B virus replication in a novel set of human hepatoma cell lines.

A panel of four novel human hepatoma cell lines was isolated from a single tumor from a male individual. BC1, B16 and B16A2 lines were well differentiated, while cells of the B9 line were only poorly differentiated, being essentially negative for the functions analyzed. These cell lines have been surveyed for expression of a large set of plasma proteins, accumulation of liver-specific mRNAs and DNA-binding activity of ubiquitous and liver-enriched transcription factors. BC1 cells expressed the highest levels of albumin mRNA, whereas B16 and B16A2 cells accumulated the largest amounts of haptoglobin mRNA. In addition, B16 and B16A2 cells were unique in that they expressed CYP2E1 mRNA, a species absent from the available human liver cells, including HepG2 hepatoma cells, and 3-methylcholanthrene-inducible CYP1A2 mRNA. The activities of genes encoding transcription factors were evidenced in all four cell lines which expressed mRNAs for nuclear factor interleukin 6 and hepatocyte nuclear factor 1 (HNF) together with the DNA-binding activity of NFY and AP1 nuclear proteins. Strikingly, HNF-1 and HNF-4-like DNA-binding activities were restricted to BC1, B16 and B16A2 cells, supporting the idea of the potential role of these (or closely related) factors in the maintenance and/or in the establishment of the differentiated phenotype. B9 cells contained variant HNF1-like DNA-binding activity, similar to dedifferentiated rat hepatoma cells of the H5 line. CCAAT/enhancer-binding protein and HNF-3-like activities were found in all cell lines, although at a lower level and/or activity in B9 cells. Finally, transfection experiments of plasmids containing the whole hepatitis-B virus genome demonstrated that B16 cells, but not B9 cells, were able to support hepatitis-B virus replication and virion production, in agreement with the notion that HNF-1 activity is necessary for viral replication. We believe that the specific complement of transcription factors expressed in the differentiated BC1, B16 and B16A2 cells, and in the poorly differentiated B9 cells, will allow studies on the regulation of hepatic gene expression in these human lines, and will also aid the analysis of xenobiotic metabolism and the biology of hepatitis-B virus replication.

Base Sequence↗
PubMed1999

Simian immunodeficiency virus disease course is predicted by the extent of virus replication during primary infection.

To elucidate the relationship between early viral infection events and immunodeficiency virus disease progression, quantitative-competitive and branched-DNA methods of simian immunodeficiency virus (SIV) RNA quantitation were cross-validated and used to measure viremia following infection of rhesus macaques with the pathogenic SIVmac251 virus isolate. Excellent correlation between the methods suggests that both accurately approximate SIV copy number. Plasma viremia was evident 4 days postinfection, and rapid viral expansion led to peak viremia levels of 10(7) to 10(9) SIV RNA copies/ml by days 8 to 17. Limited resolution of primary viremia was accompanied by relatively short, though variable, times to the development of AIDS (81 to 630 days). The persistent high-level viremia observed following intravenous inoculation of SIVmac251 explains the aggressive disease course in this model. Survival analyses demonstrated that the disease course is established 8 to 17 days postinfection, when peak viremia is observed. The most significant predictor of disease progression was the extent of viral decline following peak viremia; larger decrements in viremia were associated with both lower steady-state viremia (P = 0.0005) and a reduced hazard of AIDS (P = 0.004). The data also unexpectedly suggested that following SIVmac251 infection, animals with the highest peak viremia were better able to control virus replication rather than more rapidly developing disease. Analysis of early viral replication dynamics should help define host responses that protect from disease progression and should provide quantitative measures to assess the extent to which protective responses may be induced by prophylactic vaccination.

Animals↗
PubMed2002

Effect of lack of Interleukin-4, Interleukin-12, Interleukin-18, or the Interferon-gamma receptor on virus replication, cytokine response, and lung pathology during respiratory syncytial virus infection in mice.

RSV is an important cause of bronchiolitis in infants. Immunopathology may play a role in RSV-induced bronchiolitis and severe RSV-induced disease has been associated with a Th2 type immune response. The aim of the study was to identify cytokine pathways that are crucial in influencing RSV-induced disease. For that purpose we inoculated IFNgammaR-/-, IL-12-/-, IL-18-/-, or IL-4-/- mice with RSV. We observed that an RSV infection resulted in a predominant Th1 cytokine response associated with slight bronchiolitis and alveolitis. Pulmonary histopathology was only aggravated in IFN R-/- mice, characterised by eosinophilic influx around the bronchioles. Despite subtle changes in cytokine expression, no differences in histopathology were observed in IL-12-/- and IL-18-/- mice. Deficiency of IL-4 has no effect on RSV-induced Th1 cytokines and pulmonary histopathology. IFNgamma-receptor deficiency during primary RSV infection resulted in a disturbed Th1 response based on increased IL-4, IL-5, and IL-13 expression and the presence of eosinophils in the lungs. It is concluded that IFNgamma signalling is required for a pronounced Th1 response to RSV while IL-12 and IL-18 are not. A shift in the balance between Th1 and Th2 towards a Th2 response induced by missing IFNgamma signalling leads to aggravated pulmonary pathology. This is not caused by enhanced viral load.

Animals↗
PubMed1998

Oxygen tension and virus replication.

An evidence is accumulating that the oxygen tension exerts significant effect on the virus replication in vitro. When the in vitro oxygen tension is maintained at an in vivo physiological level, as a rule higher yields of human viruses are seen that at conventional culturing with access of an unphysiologically high oxygen concentration in ambient air. Although not fully understood, possible explanation for this phenomenon may be provided by a lowered interferon (IFN) output and increased cell replication which is often optimal at physiological oxygen tension. Furthermore, an indirect evidence suggests that the expression of some virus receptors is affected by oxygen tension. Also, the antiviral cell-mediated immunity is likely to be found oxygen tension-dependent as both the NK and cytotoxic T cell activities towards uninfected target cells are oxygen tension-sensitive. At present, the in vitro work with viruses at physiological oxygen tensions is hampered by the fact that cells adapt in the course of several weeks to the new oxygen tension. Whether viruses may adapt to different oxygen tensions is not clear. Workbenches combining safety in manipulation with hazardous viruses and the convenience of controlled gas atmosphere during both manipulation and long-term incubation have been developed. It is suggested that the in vitro virology should ensure that the physiological oxygen tension is better mimicked in the in vivo processes. Much work is to be done to determine the molecular interactions between oxygen tension-sensitive elements of the cell and infecting viruses. Of no lesser importance are the questions regarding the role of oxygen in virus tissue tropism, the cost-benefit of virus production at different oxygen tension levels, and the potential significance of oxygen tension for delivering gene effects to the selected target tissues.

Animals↗
PubMed1976

[Study of Aujeszky's disease virus replication by using an immunofluorescent method].

Studied was the interrelationship between the Aujeszky's disease virus (the avirulent mutant strain MK and the virulent strain 2) and chick embryo cells during cultivation with and without 5-iod-2-desoxiuridine. In experiments with the virulent strain the presence of a granular antigen could be observed at the 4th hour following the infection of the nucleus. After the 10th hour the antigen showed migration from the nucleus toward the cytoplasm. After the 24th hour a complete destruction of the cellular monolayer was observed, along with the production of polynuclear cells. In the experiments with strain MK the antigen seemed to appear first in the cytoplasm after the 10th hour of infecting the cells, and after the 12th hour it was found in the nucleoplasm too. In this case full destruction of the cells set in after the 48th hour of infection. In the cultivation of strain MK in cell cultures containing 5-iod-2-desoxiuridine no disturbances in the normal cycle of reproduction was observed. The virus replicated equally well both with and without the antimetabolite. In the cultivation of the virulent strain 2 in cell cultures that contained 5-iod-2-desoxiuridine a coarse, granular antigen was noticed in the cytoplasm of single cells after the eighth hour of infection. After the 12th hour the nuclei of these cells manifested slight flourescence (hardly visible single granules). After the 48th hour the nuclei of the involved cells were swollen, and the cytoplasm presented slight, diffuse fluorescence, some of the cells being destroyed.

Animals↗
PubMed1994

Oral famciclovir against duck hepatitis B virus replication in hepatic and nonhepatic tissues of ducklings infected in ovo.

Detection of hepadnaviral DNA in extrahepatic tissues of human and animal models of hepatitis B virus (HBV) has raised the question of whether virus replication in organs other than the liver could be targeted for the treatment of chronic hepatitis B. Since duck hepatitis B virus (DHBV) replication is dynamic in the liver, kidney, pancreas, and spleen of newly hatched ducklings infected in ovo, we used the duck model and the new antiherpesvirus agent, famciclovir (FCV), to determine whether antiviral effect of nucleoside analogues on DHBV replication is pluripotential. Day-old ducklings hatched from eggs laid by a DHBV-carrier duck were bled and administered FCV (25 mg/kg/bd) orally for periods of 1, 2, 3, 6, 9, and 12 days. Seventeen (17) hours after the last dose of each regimen the duckling(s) was bled and postmortem samples of liver, kidney, pancreas, and spleen were snap-frozen and stored at -70 degrees C. Analysis of plasma samples of ducklings treated for 2 days and longer by dot-blot hybridisation showed that levels of DHBV DNA were reduced significantly compared to levels in samples collected before treatment begun. Southern blot hybridisation of tissue DNA corroborated these results and showed that DHBV DNA replicative intermediates in all the tissues examined were reduced to levels that reflected the amount of virus released into the blood of each treated duckling. It is concluded from these results that if antiviral agents could be transformed to active metabolites in any infected tissues including the liver, replication of hepadnaviruses would be inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Aminopurine↗
PubMed2001

Expression of human MxA protein in mosquito cells interferes with LaCrosse virus replication.

Human MxA protein inhibits LaCrosse virus (LAC virus; family Bunyaviridae) replication in vertebrate cells and MxA-transgenic mice. LAC virus is transmitted to humans by Aedes triseriatus mosquitoes. In this report, we have shown that transfected mosquito cells expressing the human MxA cDNA are resistant to LAC virus but permissive for Sindbis virus (family Togaviridae) infection.

Aedes↗
PubMed1976

Synchronization of cowpea chlorotic mottle virus replication in cowpea leaves.

A technique that 'systemically inoculates' cowpea leaves with cowpea chlorotic mottle virus (CCMV) is described. The upper leaves of cowpea plants are maintained at 10 degrees and allowed to become infected with inoculum from lower leaves maintained at 32 degrees; when the whole plant is shifted to 25 degrees, synchronous virus replication starts in the upper leaves. Following the shift to 25 degrees, no infectivity could be detected during the first 6 h, after which the infectivity increased exponentially between 8 and 20 h and linearly between 20 and 72 h. The time-courses of effectiveness of different inhibitors occurred sequentially and at different times during the infection. An actinomycin-D-sensitive step occurred at 10 degrees, prior to the shift to 25 degrees. A 2.0 mM guanidine-sensitive step occurred between 4 and 20 h and a cycloheximide-sensitive step occurred between 12 and 48 h after the shift to 25 degrees. When the upper leaves were maintained at 5 degrees while the infected lower leaves were at 32 degrees, viral inoculum did not move into them. However, rapid systemic infection occurred during the first 6 h after a shift of the whole plant to 25 degrees.

Cycloheximide↗
PubMed1988

Suppression of BK virus replication and cytopathic effect by inhibitors of prokaryotic DNA gyrase.

Nalidixic acid and oxolinic acid, two antibacterial agents known to inhibit bacterial DNA gyrase, are shown to suppress the replication, as well as the cytopathic effect, of BK virus in Vero cell cultures. The inhibition of virus replication was detectable at day 4 post infection in cultures which had been continuously exposed to drugs at concentrations as low as 0.02 to 0.04 mM of nalidixic acid and 0.2 mM of oxolinic acid. These active concentrations are inferior to plasma levels attained in the course of clinical use of the drugs for antibacterial chemotherapy. Also, under these circumstances, no cytotoxicity occurred. The inhibition of development of cytopathology and of virus-induced cell death was demonstrable in cultures treated for 12 days with the drugs. Under these circumstances of prolonged action, oxolinic acid proved to be slightly cytotoxic in that virus inhibitory doses reduced the viability of normal cells. No alterations in the topological conformation of the viral genome or accumulation of end products of viral DNA replication were detected. However, accumulation of viral DNA form I at 48 h post infection suggests that the drugs act through a mechanism involving DNA topoisomerase.

Antigens, Viral↗
PubMed2004

Assembly of turnip yellow mosaic virus replication complexes: interaction between the proteinase and polymerase domains of the replication proteins.

Turnip yellow mosaic virus (TYMV), a positive-strand RNA virus in the alphavirus-like supergroup, encodes two nonstructural replication proteins (140K and 66K), both of which are required for its RNA genome replication. The 140K protein contains domains indicative of methyltransferase, proteinase, and NTPase/helicase activities, while the 66K protein encompasses the RNA-dependent RNA polymerase domain. Recruitment of the 66K protein to the sites of viral replication, located at the periphery of chloroplasts, is dependent upon the expression of the 140K protein. Using antibodies raised against the 140K and 66K proteins and confocal microscopy, we report the colocalization of the TYMV replication proteins at the periphery of chloroplasts in transfected or infected cells. The replication proteins cofractionated in functional replication complexes or with purified chloroplast envelope membranes prepared from infected plants. Using a two-hybrid system and coimmunoprecipitation experiments, we also provide evidence for a physical interaction of the TYMV replication proteins. In contrast to what has been found for other members of the alphavirus-like supergroup, the interaction domains were mapped to the proteinase domain of the 140K protein and to a large region encompassing the core polymerase domain within the 66K protein. Coexpression and colocalization experiments confirmed that the helicase domain of the 140K protein is unnecessary for the proper recruitment of the 66K protein to the chloroplast envelope, while the proteinase domain appears to be essential for that process. These results support a novel model for the interaction of TYMV replication proteins and suggest that viruses in the alphavirus-like supergroup may have selected different pathways to assemble their replication complexes.

Arabidopsis↗
PubMed1996

A bispecific antibody recognizing influenza A virus M2 protein redirects effector cells to inhibit virus replication in vitro.

Bispecific antibodies can be used to redirect cytotoxic T cells to kill virus-infected cells, overriding the need for major histocompatibility complex restriction. We produced a bispecific antibody (3F12) which binds influenza virus M2 protein and the T-cell receptor and can redirect staphylococcal enterotoxin B-activated T cells to kill influenza virus-infected cells and inhibit virus replication in vitro.

Amino Acid Sequence↗
PubMed2004

Role of cytoskeleton components in measles virus replication.

Cellular factors have been indicated to be essential for the replication of Measles virus (MV), but the exact roles of these components are, however, not understood in detail. In this study, we investigated the role of actin and tubulin in productive MV infection by inducing disassembly of the microfilaments and microtubules. Vero cells were treated with latrunculin-A, which sequesters actin monomers, or nocodazole, which breaks the microtubules. The disruption of either of the structures efficiently inhibited the maturation of new infectious virus. Interestingly, virus spreading to neighboring cells still occurred by fusion and large syncytia typical for MV infection appeared. We also investigated a possible role for proteins of the ERM-family. Our results support an important role for actin filaments and microtubules for efficient MV replication.

Actin Cytoskeleton↗
PubMed1996

Induction of HSP70 and polyubiquitin expression associated with plant virus replication.

By examining the front of virus invasion in immature pea embryos infected with pea seed-borne mosaic virus (PSbMV), the selective control of different host genes has been observed. From our observations, the early responses to PSbMV replication can be grouped into three classes, inhibited host gene expression, induced host gene expression, and no effect on a normal host function. The expression of two heat-inducible genes encoding HSP70 and polyubiquitin was induced coordinately with the onset of virus replication and the down-regulation of two other genes encoding lipoxygenase and heat shock cognate protein. The down-regulation was part of a general suppression of host gene expression that may be achieved through the degradation of host transcripts. We discuss the possibilities of whether the induction of HSP70 and polyubiquitin genes represents a requirement for the respective protein products by the virus or is merely a consequence of the depletion of other host transcripts. The former is feasible, as the induction of both genes does result in increased HSP70 and ubiquitin accumulation. This also indicates that, in contrast to some animal virus infections, there is not a general inhibition of translation of host mRNAs following PSbMV infection. This selective control of host gene expression was observed in all cell types of the embryo and identifies mechanisms of cellular disruption that could act as triggers for symptom expression.

Biopolymers↗