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At least 253 records · Page 14Linked to original sources
PubMed1985

Effect of human alpha A interferon on influenza virus replication in MDBK cells.

To determine the molecular mechanism whereby interferon induces resistance to influenza virus, we began an investigation of influenza virus replication in MDBK cells treated with recombinant human alpha A interferon. Negative- and positive-strand virus-specific RNA accumulation was monitored by blot hybridization with cloned probes. Primary transcription (transcription of infecting viral negative strands by the virion-associated polymerase) was inhibited by interferon treatment of MDBK cells. At moderate levels of interferon treatment (10 U/ml), this inhibition was restricted to transcripts of polymerase genes, whereas at higher levels of interferon treatment (50 U/ml), accumulation of all primary transcripts was markedly inhibited. Secondary transcripts and viral negative strands did not accumulate to any significant extent in interferon-treated MDBK cells. These results suggest that interferon-induced mechanisms which inhibit influenza virus replication in MDBK cells act at the level of primary transcription.

Animals↗
PubMed1985

Herpes simplex virus 1 reiterated S component sequences (c1) situated between the a sequence and alpha 4 gene are not essential for virus replication.

The herpes simplex virus 1 genome consists of two components, L and S, each containing unique sequences flanked by inverted repeats. Each of the 6.5-kilobase pair inverted repeats of the S component, designated a'c' and ca, contains an approximately 700-base pair sequence (designated c1) located between the a sequence and the 3' terminus of the alpha 4 gene. Like the a sequence, c1 consists of direct repeats and unique sequences. Its function is not known. To probe for its function, we constructed a plasmid containing a viral thymidine kinase (TK) gene inserted into the c1 sequence. The construct was recombined into the genome of a TK- virus by cotransfection with intact viral DNA and selection for TK+ virus. As predicted from previous studies (Knipe et al., Proc. Natl. Acad. Sci. U.S.A. 75:3896-3900, 1978), the TK gene was found to be present in both copies of the c1 sequence in the R3104 virus. To delete the c1 sequence we constructed a plasmid containing 4 kilobase pairs of pBR322 flanked by an a sequence and by structural sequences of the alpha 4 gene. In this instance the cells were transfected with the construct and R3104 DNA; the progeny of the transfection was plated in the presence of 5-bromo-2'-deoxyuridine, and the selection was for TK- virus (R3158). The pBR322 DNA sequences replaced the c1 at both termini of the S component in R3158 DNA, but a sequence homologous to c1 was present in proximity to the 3' terminus of the alpha 4 gene. The results indicate that the c1 region has no significant role in the replication of the virus in cell culture. The advantage of inserting the pBR322 sequence is that it permits efficient cloning of large herpes simplex virus 1 DNA fragments by simple ligation of digests and transformation of appropriate Escherichia coli strains. The effortless selection of recombinants carrying inserts in both copies of the c1 restates the usefulness of this technique for selection of insertion deletion recombinants and underscores the rapid emergence of sequence identity at both ends of the reiterated regions of the S component as previously reported (Knipe et al., Proc. Natl. Acad. Sci. U.S.A. 75:3896-3900, 1978).

DNA, Viral↗
PubMed1991

Expression of X protein and hepatitis B virus replication in chronic hepatitis.

The X protein can act on the enhancer of hepatitis B virus in an in vitro system and elevate the transcriptional level of hepatitis B virus. However, because no relationship had been reported between X protein expression and hepatitis B virus replication in patients with chronic hepatitis B, we focused on its expression in the liver in comparison with markers of hepatitis B virus replication. Liver biopsy samples and sera from 59 carriers with HBsAg were examined immunohistochemically for X protein using rabbit IgG against recombinant X protein. There was a significant difference in the serum hepatitis B virus DNA level between X protein-positive and -negative patients (p less than 0.001). Serum pre-S1 and pre-S2 antigens were also measured quantitatively by enzyme immunoassay using monoclonal antibodies specific against each antigen. The titers of pre-S1 antigen in patients positive for X protein were significantly higher (p less than 0.001) than those of the X protein-negative patients (3.02 +/- 0.99 vs. 2.00 +/- 0.59, respectively). Similarly, the titers of pre-S2 antigen were 2.98 +/- 0.91 vs. 1.94 +/- 0.54, respectively (p less than 0.001). The rate of positivity of the X protein was higher (38 of 49; 77.6%) in the replicative group (serum HBeAg, serum hepatitis B virus DNA or HBcAg in liver positive) compared with that observed in the nonreplicative group (3 of 10; 30%--serum HBeAg, serum hepatitis B virus DNA and HBcAg in liver negative) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1996

Mutagenesis of the N-linked glycosylation sites of the yellow fever virus NS1 protein: effects on virus replication and mouse neurovirulence.

The flavivirus nonstructural glycoprotein NS1 is highly conserved and contains two N-linked glycosylation sites which are both utilized for addition of oligosaccharides during replication in cell culture. NS1 has been shown to contain epitopes for protective antibodies; however, its roles in virus replication and pathogenesis remain unknown. To study the function of NS1 during yellow fever virus replication, six mutant viruses which lack either one or both glycosylation sites and another one containing silent mutations at both sites were generated by site-directed mutagenesis. Mutants lacking the second glycosylation site and those bearing silent mutations were similar to the parental virus in their cell culture properties. Ablation of the first or both glycosylation sites generated mutants exhibiting small plaque phenotypes, decreased virus yields, reduced cytopathic effects, impaired NS1 secretion, and depressed RNA accumulation. In addition, mutants lacking the first or both glycosylation sites exhibited significant reduction in mouse neurovirulence after intracerebral inoculation. These defects appear to result from the lack of N-linked glycans rather than the introduction of deleterious amino acid substitutions or disruption of cis-acting RNA elements important for RNA replication. These results suggest an important role for NS1 in flavivirus RNA replication and pathogenesis.

Animals↗
PubMed1974

Mechanism of Sindbis virus-induced intrinsic interference with vesicular stomatitis virus replication.

Heterologous viral interference is induced by Sindbis virus against vesicular stomatitis virus (VSV) in a manner analogous to intrinsic interference with Newcastle disease virus replication. Interference in both systems (i) depends upon early expression of the inducing virus genome, (ii) shows similar kinetics of induction, (iii) does not involve interferon action, and (iv) appears to be manifest as an all-or-none effect. VSV can be added to the list of viruses blocked by intrinsic interference. Sindbis virus-induced intrinsic interference with VSV replication is not mediated through homotypic interference by defective interfering particles; rather, T-particle and B-particle synthesis is inhibited. Significantly, intrinsic interference has no effect on primary transcription directed by the virion-associated transcriptase in VSV-challenged cells. However, Sindbis virus appears to induce interference with the VSV-RNA synthesized subsequent to primary transcription, namely, that which is dependent on protein synthesis. Thus, the target of intrinsic interference appears to be a reaction subsequent to primary transcription but prior to the appearance of protein synthesis-dependent VSV RNA, secondary transcription.

Animals↗
PubMed1996

Calcium spirulan, an inhibitor of enveloped virus replication, from a blue-green alga Spirulina platensis.

Bioactivity-directed fractionation of a hot H2O extract from a blue-green alga Spirulina platensis led to the isolation of a novel sulfated polysaccharide named calcium spirulan (Ca-SP) as an antiviral principle. This polysaccharide was composed of rhamnose, ribose, mannose, fructose, galactose, xylose, glucose, glucuronic acid, galacturonic acid, sulfate, and calcium. Ca-SP was found to inhibit the replication of several enveloped viruses, including Herpes simplex virus type 1, human cytomegalovirus, measles virus, mumps virus, influenza A virus, and HIV-1. It was revealed that Ca-SP selectively inhibited the penetration of virus into host cells. Retention of molecular conformation by chelation of calcium ion with sulfate groups was suggested to be indispensable to its antiviral effect.

Antiviral Agents↗
PubMed1981

Adeno-associated virus replication. The effect of L-canavanine or a helper virus mutation on accumulation of viral capsids and progeny single-stranded DNA.

We have studied the relationship between adeno-associated virus (AAV) DNA replication and virus particle assembly. Formation of empty or full particles and accumulation of AAV capsid proteins was prevented in the presence of the arginine analogue, L-canavanine, or when a temperature-sensitive helper adenovirus was used at the nonpermissive temperature. In each case there was a concomitant inhibition of AAV single-stranded (progeny) DNA accumulation but little or no effect upon synthesis of AAV duplex, replicating form DNA. These results indicate that AAV protein, perhaps in the form of assembled capsids, is required for AAV single-stranded progeny DNA accumulation.

Canavanine↗
PubMed2005

Inhibition of influenza A virus replication by resveratrol.

We have previously shown that the life cycles of several viruses are influenced by host-cell redox states. Reports of the antioxidant activities of the plant polyphenol resveratrol (RV) prompted us to investigate its effects on influenza virus replication in vitro and in vivo. We found that RV strongly inhibited the replication of influenza virus in MDCK cells but that this activity was not directly related to glutathione-mediated antioxidant activity. Rather, it involved the blockade of the nuclear-cytoplasmic translocation of viral ribonucleoproteins and reduced expression of late viral proteins seemingly related to the inhibition of protein kinase C activity and its dependent pathways. RV also significantly improved survival and decreased pulmonary viral titers in influenza virus-infected mice. No toxic effects were observed in vitro or in vivo. That RV acts by inhibiting a cellular, rather than a viral, function suggests that it could be a particularly valuable anti-influenza drug.

Animals↗
PubMed1983

Studies on the mechanism of temperature sensitivity of infectious pancreatic necrosis virus replication.

Yields of infectious pancreatic necrosis virus from fathead minnow cell cultures were maximal at 20 degrees C. The virus failed to replicate at 28 degrees C and neither virus-specific mRNA nor virus-specific polypeptides could be detected when infected cells were maintained at this temperature. Intrinsic thermolability of virus infectivity or inability to adsorb to cells at 28 degrees C could not account for the temperature-dependent block in virus morphogenesis. Analysis of infectious virus production and virus-specific polypeptide and RNA synthesis following shifts from the permissive (20 degrees C) to the non-permissive temperature (28 degrees C) at various times after infection indicated that multiple temperature-sensitive (ts) steps were involved in the inhibition of virus replication.

Animals↗
PubMed1998

The role of herpes simplex virus glycoproteins in the virus replication cycle.

At least nine of the eleven herpes simplex virus (HSV) glycoproteins so far known have been widely characterised as regards their role in the virus replication cycle. During early virus-to-cell adsorption ("adsorption"), glycoprotein C (gC) interacts with the glycosoaminoglycan (GAG) heparan sulphate (HS), located on the cell membrane surface. This interaction is labile until other glycoproteins such as B and D (gB and gD) begin to participate in the entry process. gB also harbours a site for interaction with GAGs, while gD provides a stabile attachment to cellular receptors ("receptors") such as the herpesvirus entry mediator (HVEM). Late adsorption is associated with a conformation change of gD occurring after the receptor binding, a step followed by interaction of gD with the gH/gL heterodimer (complex). Fusion domains of the gH/gL complex and gB enable the pH-independent virus-into-cell penetration ("penetration"). The gE/gI complex and gM interact with the receptors at cell junctions in order to facilitate cell-to-cell spread of the virus along the basolateral surface of polarised cells and/or a similar intercellular spread in nonpolarised cells by avoiding virion release, gK, the only so far known HSV-coded glycoprotein which is not incorporated into virions, plays an essential role in the virus capsid envelopment at the nuclear membrane and in the virion transport to the cell surface. Unusually large polykaryocytes arise due to mutations in syn (syncytium) loci of the viral genome, which were mapped to UL53 (syn1) and UL27 (syn3) genes coding for gK and gB, respectively, while the genes UL20 and UL24 (both syn5) code for nonglycosylated cell membrane-associated proteins ("membrane proteins"). The products of nonmutated syn genes either downregulate the fusion of plasma membranes of infected cells ("membrane fusion") or protect them from undesirable fusion events.

Adsorption↗
PubMed2006

Downregulation of varicella-zoster virus (VZV) immediate-early ORF62 transcription by VZV ORF63 correlates with virus replication in vitro and with latency.

Varicella-zoster virus (VZV) open reading frame 63 (ORF63) protein is expressed during latency in human sensory ganglia. Deletion of ORF63 impairs virus replication in cell culture and establishment of latency in cotton rats. We found that cells infected with a VZV ORF63 deletion mutant yielded low titers of cell-free virus and produced very few enveloped virions detectable by electron microscopy compared with those infected with parental virus. Microarray analysis of cells infected with a recombinant adenovirus expressing ORF63 showed that transcription of few human genes was affected by ORF63; a heat shock 70-kDa protein gene was downregulated, and several histone genes were upregulated. In experiments using VZV transcription arrays, deletion of ORF63 from VZV resulted in a fourfold increase in expression of ORF62, the major viral transcriptional activator. A threefold increase in ORF62 protein was observed in cells infected with the ORF63 deletion mutant compared with those infected with parental virus. Cells infected with ORF63 mutants impaired for replication and latency (J. I. Cohen, T. Krogmann, S. Bontems, C. Sadzot-Delvaux, and L. Pesnicak, J. Virol. 79:5069-5077, 2005) showed an increase in ORF62 transcription compared with those infected with parental virus. In contrast, cells infected with an ORF63 mutant that is not impaired for replication or latency showed ORF62 RNA levels equivalent to those in cells infected with parental virus. The ability of ORF63 to downregulate ORF62 transcription may play an important role in virus replication and latency.

Adenoviridae↗
PubMed1993

Inhibition of vesicular stomatitis virus replication by delta 12-prostaglandin J2 is regulated at two separate levels and is associated with induction of stress protein synthesis.

delta 12-Prostaglandin J2 (delta 12-PGJ2), a naturally occurring dehydration product of prostaglandin D2, is shown to suppress the replication of vesicular stomatitis virus (VSV) in two different epithelial monkey cell lines. A significant delay in the virus-induced cytopathic effect and a dramatic inhibition of virus production can be obtained at doses which do not inhibit protein synthesis in uninfected cells, and induce the synthesis of heat shock proteins (HSPs) in both uninfected and VSV-infected cells. delta 12-PGJ2 is shown to block VSV replication at two separate levels in the early and late phase of the virus replication cycle. Treatment started soon after VSV infection greatly suppresses viral (but not cellular) protein synthesis and prevents the virus-induced shut-off of host cell protein synthesis. This effect is accompanied by the induction of HSP synthesis. delta 12-PGJ2-treatment in a late phase of the virus replication cycle, when all virus proteins have been synthesized, still causes a dramatic block of infectious virus production. This block is accompanied by a decrease in [3H]glucosamine incorporation into the virus glycoprotein G, at concentrations which do not alter glucosamine uptake by the cells, suggesting that a defect in virus protein glycosylation could be responsible for the antiviral activity. Finally, delta 12-PGJ2 causes a decrease of glucosamine incorporation into at least two host cell polypeptides, while the majority of cellular proteins are unaffected and glycosylation of a 47 kDa cellular protein is strongly induced. These selective alterations of protein glycosylation suggest that delta 12-PGJ2 affects a specific group of glycosylated proteins. The finding that cyclopentenone prostaglandins act on different events during the virus cycle explains the effectiveness of these compounds in controlling the replication of different types of viruses and presents an attractive new approach to antiviral chemotherapy.

Animals↗
PubMed1987

Accumulation and chemotaxis of natural killer/large granular lymphocytes at sites of virus replication.

A model for monitoring the accumulation of natural killer cell/large granular lymphocytes (NK/LGL) at a site of virus replication was studied by using mice infected i.p. with either lymphocytic choriomeningitis virus (LCMV), murine cytomegalovirus (MCMV), mouse hepatitis virus (MHV), Pichinde virus, or vaccinia virus. An i.p. but not i.v. infection resulted in a localized increase in NK/LGL cell number (a fourfold to greater than 20-fold increase) and augmentation (a 10- to 20-fold increase) of NK cell activity associated with virus-induced peritoneal exudate cell (PEC) populations. An increase in NK/LGL cell number was detected as early as 12 hr postinfection (p.i.) and peaked at 3 days p.i. with MHV. The initial LGL recruited into the peritoneal cavity at 1 to 3 days p.i. were nonadherent to plastic and were demonstrated to have an NK cell phenotype: asialo GM1+, Thy-1.2 +/-, Lyt-2.2-, and J11d-. The peak number of LGL appeared at 7 days after infection with the NK cell-resistant virus, LCMV. This LGL population had been previously demonstrated to contain cytotoxic T lymphocyte/LGL (CTL/LGL) as well as NK/LGL. During an MHV infection the number of LGL decreased between days 3 and 7 p.i., suggesting that the second wave of CTL/LGL was absent. These findings may explain the absence of a good MHV-CTL model. Virus-induced, activated NK/LGL responded to chemotactic signals by migrating in a unidirectional manner across two 5-microns pore size polycarbonate filters during 7 hr in vitro chemotaxis assays. Wash-out fluid obtained from the peritoneal cavity contained chemotactic activity for NK/LGL as well as for other cell types. We conclude that production and/or release of chemotactic factors at sites of virus replication are at least partially responsible for the accumulation of NK/LGL at these sites.

Animals↗
PubMed1981

Prostaglandins of the A series inhibit Sendai virus replication in cultured cells.

Prostaglandins of the A series (PGA) were shown to be potent inhibitors of Sendai virus replication in African green monkey kidney cells in culture. This antiviral activity was specific for PGA. The effective dose (4 micrograms/ml) was not toxic to the cells and did not alter either host cell metabolism of infectivity of the virus. PGA did not affect the first stages of virus replication and seemed to act by inhibiting virus maturation and/or budding from the cells. The antiviral action of PGA was pharmacological, was not mediated by cAMP and was completely reversible. Possible mechanisms of action include post-translational binding to virus proteins or interaction with interferon.

Animals↗
PubMed1986

Pseudotyped retroviral vectors reveal restrictions to reticuloendotheliosis virus replication in rat cells.

Reticuloendotheliosis viruses (Rev) replicate in chicken and dog cells, but not in rat cells. Amphotropic murine leukemia viruses (Am-MLV) replicate in chicken, dog, and rat cells. Transcription from the Rev long terminal repeat, determined by the chloramphenicol acetyltransferase assay, was not significantly different from transcription from the MLV long terminal repeat in rat cells. To determine further the step(s) in the retroviral life cycle that is blocked for Rev replication in rat cells, we took advantage of the wide host range of Am-MLV (S. Rasheed, M. B. Gardner, and E. Chan, J. Virol. 19:13-18, 1976) and the ability to form Rev-Am-MLV pseudotypes. Data from these pseudotypes indicate that the block to Rev replication in rat cells is posttranscriptional.

Animals↗