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Results for “Virus Replication”

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At least 559 records · Page 31Linked to original sources

PubMed1991

BHRF1, the Epstein-Barr virus gene with homology to Bc12, is dispensable for B-lymphocyte transformation and virus replication.

The Epstein-Barr virus (EBV) BHRF1 open reading frame is abundantly expressed early in the lytic replication cycle. BHRF1 is also transiently expressed in some latently infected cell lines in the absence of expression of other lytic cycle proteins. BHRF1 shares distant, but significant, colinear primary amino acid sequence homology to Bc12, a cellular gene strongly implicated in the evolution of follicular lymphoma. The experiments reported here used a molecular genetic approach to examine the role of BHRF1 in EBV infection. Isogenic EBV recombinants having either wild-type BHRF1 or a null mutation due to a translational stop signal in place of the 24th BHRF1 codon were used to infect primary B lymphocytes. The BHRF1 mutant recombinants did not differ from the wild type in their ability to infect and transform the growth of primary B lymphocytes, to replicate in the resultant lymphoblastoid cell lines, or to initiate a second round of primary cell transformation. Deletion of the entire BHRF1 open reading frame did not destroy the ability of the mutant virus to maintain cell growth transformation. The significance of these findings with regard to the role of BHRF1 in EBV infection is discussed.

B-Lymphocytes↗

PubMed1992

Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication.

We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.

Animals↗

PubMed2001

Broad distribution of the JC virus receptor contrasts with a marked cellular restriction of virus replication.

To investigate the early events of JC virus (JCV) infection, including attachment, penetration, transport to the nuclei, and replication of the virus, we analyzed the susceptibility of 15 different cell lines to infection using a semiquantitative polymerase chain reaction (PCR) assay, in situ hybridization, laser scanning confocal microscopy, and a viral replication assay. The cell lines examined were human permissive and nonpermissive cells as well as cells of monkey and mouse origin. JCV entry into the nuclei of the all cell lines was observed within 10 min after inoculation, demonstrating that the virus receptor is widely distributed among mammalian cells. Inhibition of viral entry by an anti-JCV VP1 antibody and sialidase treatment to remove sialic acid residues, which are considered a candidate for the JCV receptor, suggested that VP1 may interact with the cellular surface sialic acid. In addition, chlorpromazine, a clathrin-dependent pathway inhibitor, significantly suppressed entry of JCV into nuclei. In spite of the broad spectrum of cells susceptible to JCV entry, replication of the virus occurred exclusively in human neuroblastoma cell lines. These results suggest that whereas JCV can enter a wide variety of cell types and localize to the nuclei, cell-specific intranuclear mechanisms are required for virus replication.

HeLa Cells↗

PubMed2002

Inhibition of hepatitis B virus replication by interferon requires proteasome activity.

Hepatitis B virus (HBV) replication is inhibited in a noncytopathic manner by alpha/beta interferon (IFN-alpha/beta) and IFN-gamma. We demonstrate here that inhibitors of cellular proteasome activity can block this antiviral effect. These results suggest that a critical component of the IFN-induced antiviral response may be the proteasome-dependent degradation of viral or cellular proteins that are required for HBV replication.

Adenosine Triphosphatases↗

PubMed2006

Cell cycle perturbations induced by infection with the coronavirus infectious bronchitis virus and their effect on virus replication.

In eukaryotic cells, cell growth and division occur in a stepwise, orderly fashion described by a process known as the cell cycle. The relationship between positive-strand RNA viruses and the cell cycle and the concomitant effects on virus replication are not clearly understood. We have shown that infection of asynchronously replicating and synchronized replicating cells with the avian coronavirus infectious bronchitis virus (IBV), a positive-strand RNA virus, resulted in the accumulation of infected cells in the G2/M phase of the cell cycle. Analysis of various cell cycle-regulatory proteins and cellular morphology indicated that there was a down-regulation of cyclins D1 and D2 (G1 regulatory cyclins) and that a proportion of virus-infected cells underwent aberrant cytokinesis, in which the cells underwent nuclear, but not cytoplasmic, division. We assessed the impact of the perturbations on the cell cycle for virus-infected cells and found that IBV-infected G2/M-phase-synchronized cells exhibited increased viral protein production when released from the block when compared to cells synchronized in the G0 phase or asynchronously replicating cells. Our data suggested that IBV induces a G2/M phase arrest in infected cells to promote favorable conditions for viral replication.

Animals↗

PubMed2002

Inhibition of tobacco mosaic virus replication in lateral roots is dependent on an activated meristem-derived signal.

Viral invasion of the root system of Nicotiana benthamiana was studied noninvasively with a tobacco mosaic virus (TMV) vector expressing the green-fluorescent protein (GFP). Lateral root primordia, which developed from the pericycle of primary roots, became heavily infected as they emerged from the root cortex. However, following emergence, a progressive wave of viral inhibition occurred that originated in the lateral-root meristem and progressed towards its base. Excision of source and sink tissues suggested that the inhibition of virus replication was brought about by the basipetal movement of a root meristem signal. When infected plants were inoculated with tobacco rattle virus (TRV) expressing the red-fluorescent protein, DsRed, TRV entered the lateral roots and suppressed the host response, leading to a reestablishment of TMV infection in lateral roots. By infecting GFP-expressing transgenic plants with TMV carrying the complementary GFP sequence it was possible to silence the host GFP, leading to the complete loss of fluorescence in lateral roots. The data suggest that viral inhibition in lateral roots occurs by a gene-silencing-like mechanism that is dependent on the activation of a lateral-root meristem.

Gene Silencing↗

PubMed2000

Stimulation of dengue virus replication in cultured Aedes albopictus (C6/36) mosquito cells by the antifungal imidazoles ketoconazole and miconazole.

Replication of dengue type 3 virus in Aedes albopictus C6/36 cells was enhanced more than 50-fold by addition of the antifungal imidazole derivative ketoconazole within the first 4 h of infection. The stimulatory effect was reflected in the yield of infectious virus and in levels of viral RNA and protein synthesis. Enhanced yields were observed also for other flaviviruses, including dengue type 2 virus and Murray Valley encephalitis virus. Increased yields of dengue type 3 virus were not observed in African green monkey kidney (Vero) cells, human monocytic (U-937) cells, or cells of the mosquito Toxorhynchites amboinensis (TRA-171).

Aedes↗

PubMed1995

Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus replication.

Gamma interferon (IFN-gamma)-induced nitric oxide synthase (iNOS) and nitric oxide (NO) production in the murine macrophage-like RAW 264.7 cells were previously shown to inhibit the replication of the poxviruses vaccinia virus (VV) and ectromelia virus and herpes simplex virus type 1. In the current study, we performed biochemical analyses to determine the stage in the viral life cycle blocked by IFN-gamma-induced NO. Antibodies specific for temporally expressed viral proteins, a VV-specific DNA probe, and transmission electron microscopy were used to show that the cytokine-induced NO inhibited late protein synthesis, DNA replication, and virus particle formation but not expression of the early proteins analyzed. Essentially similar results were obtained with hydroxyurea and cytosine arabinoside, inhibitors of DNA replication. Enzymatically active iNOS was detected in the lysates of IFN-gamma-treated but not in untreated RAW 264.7 cells. The IFN-gamma-treated RAW 264.7 cells which express iNOS not only were resistant to productive infection but also efficiently blocked the replication of VV in infected bystander cells of epithelial origin. This inhibition was arginine dependent, correlated with nitric production in cultures, and was reversible by the NOS inhibitor N omega-monomethyl-L-arginine.

Amino Acid Oxidoreductases↗

PubMed1995

Effect of immunosuppressive and antiviral agents on hepatitis B virus replication in vitro.

Hepatitis B virus (HBV) DNA-transfected hepatoma cells were incubated with the immunosuppressive agents prednisolone, azathioprine, and cyclosporin A (CsA) and the antiviral agents ganciclovir and foscarnet to investigate the effects of these compounds on HBV replication. Prednisolone and azathioprine increased intracellular viral DNA and RNA levels approximately twofold and fourfold, respectively. Treatment with CsA did not alter the levels of viral RNA or DNA. A combination of all three immunosuppressive agents increased the level of intracellular viral DNA eightfold, indicating an additive effect. Incubation of the cells in the presence of foscarnet decreased levels of both single-stranded and relaxed circular viral DNA, and in the presence of ganciclovir decreased the levels of relaxed circular viral DNA, predictable effects from their known mechanism of action. The stimulatory effect on viral replication induced by the combination of immunosuppressive agents was substantially inhibited by ganciclovir-foscarnet treatment. These observations could have implications for the management of recurrent HBV infection after liver transplantation.

Antiviral Agents↗

PubMed1997

The Epstein-Barr virus glycoprotein 110 carboxy-terminal tail domain is essential for lytic virus replication.

To investigate the importance of the Epstein-Barr virus (EBV) glycoprotein 110 (gp110) tail domain in the intracellular localization of gp110 and virus lytic replication, three carboxy-terminal truncation mutants of gp110 were constructed. Deletion of 16 amino acids from the carboxyl-terminal tail resulted in gp110 intracellular localization which was indistinguishable from that of wild-type gp110, whereas deletion of either 41 or 56 amino acids from the carboxyl-terminal tail of gp110 resulted in loss of retention of gp110 in the endoplasmic reticulum and nuclear membrane. None of the gp110 truncation mutants was able to complement EBV(gp110-)+ lymphoblastoid cell lines in transformation assays, indicating the importance of the gp110 tail domain in virus lytic replication. In electron microscopy analysis, no nucleocapsids or enveloped viruses were detected in EBV(gp110-)+ lymphoblastoid cell lines induced for lytic replication.

Amino Acid Sequence↗

PubMed2002

1-beta-D-arabinofuranosylcytosine inhibits borna disease virus replication and spread.

Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that causes neurological diseases in a variety of warm-blooded animal species. There is general consensus that BDV can also infect humans, being a possible zoonosis. Although the clinical consequences of human BDV infection are still controversial, experimental BDV infection is a well-described model for human neuropsychiatric diseases. To date, there is no effective treatment against BDV. In this paper, we demonstrate that the nucleoside analog 1-beta-D-arabinofuranosylcytosine (Ara-C), a known inhibitor of DNA polymerases, inhibits BDV replication. Ara-C treatment inhibited BDV RNA and protein synthesis and prevented BDV cell-to-cell spread in vitro. Replication of other negative-strand RNA viruses such as influenza virus or measles virus was not inhibited by Ara-C, underscoring the particularity of the replication machinery of BDV. Strikingly, Ara-C treatment induced nuclear retention of viral ribonucleoparticles. These findings could not be attributed to known effects of Ara-C on the host cell, suggesting that Ara-C directly inhibits the BDV polymerase. Finally, we show that Ara-C inhibits BDV replication in vivo in the brain of infected rats, preventing persistent infection of the central nervous system as well as the development of clinical disease. These findings open the way to the development of effective antiviral therapy against BDV.

Animals↗

PubMed1988

Effect of interferon-alpha, interferon-gamma and tumour necrosis factor on African swine fever virus replication in porcine monocytes and macrophages.

Bovine interferon-alpha I1 (IFN-alpha I1) and porcine interferon-gamma (IFN-gamma) inhibited African swine fever virus replication in both porcine monocytes and alveolar macrophages. The most potent antiviral activity was observed with IFN-gamma-treated alveolar macrophages. The production of both a virulent (CC83) and a non-virulent (BA71) isolate of the virus was inhibited. Bovine tumour necrosis factor alpha did not show antiviral activity in either monocytes or alveolar macrophages. Rather, an increase of African swine fever virus production in tumour necrosis factor alpha-treated monocytes was found. An analysis of viral protein synthesis in IFN-alpha I1- and IFN-gamma-treated alveolar macrophages showed an inhibition of synthesis of some viral proteins. The inhibition of late proteins was very pronounced in IFN-gamma-treated cells, and it was probably a consequence of the inhibition of African swine fever virus DNA polymerase activity.

African Swine Fever Virus↗

PubMed1982

Immunoperoxidase labeling of canine distemper virus replication cycle in Vero cells.

An indirect immunocytochemical labeling technique, using horseradish peroxidase-conjugated antibody was used to detect the intracellular and surface membrane localization of canine distemper virus (R252-CDV) antigens during productive virus replication in infected Vero cells. Specific labeling of intracellular viral antigens was restricted to rough nucleocapsid aggregates. Surface membrane labeling correlated directly with the appearances both of virus-specific membrane spikes and buds and of mature virions. Syncytial cell formation was associated with labeled cytoplasmic nucleocapsid, but there was no evidence of productive CDV formation on surface membranes. The immunoperoxidase technique provided precise ultrastructural antigenic localization with concomitant preservation of excellent ultrastructural detail within single virus-infected cells during CDV replication cycle in vitro.

Animals↗

PubMed1996

A splice hepadnavirus RNA that is essential for virus replication.

According to the current model of hepadnavirus gene expression, the viral envelope proteins are produced from unspliced subgenomic RNAs, in contrast to the retroviral mechanism, where the subgenomic env RNA is generated by RNA splicing. We now describe and characterize a novel duck hepatitis B virus RNA species which is derived from the RNA pregenome by loss of a 1.15 kb intron. This RNA (termed spliced L RNA) codes for the large surface protein (L protein), as does the previously described unspliced mRNA (the preS RNA); however, it differs in 5' leader sequence and promoter control. Mutational analysis indicates that the spliced L RNA is functionally important for virus replication in infected hepatocytes and ducks, but not for virus formation from transfected DNA genomes. This suggests that the newly discovered second pathway for L protein synthesis plays a distinct role in an early step in the viral life cycle.

Animals↗

PubMed1999

Envelope-dependent restriction of human immunodeficiency virus type 1 spreading in CD4(+) T lymphocytes: R5 but not X4 viruses replicate in the absence of T-cell receptor restimulation.

The human immunodeficiency virus (HIV) replicates in activated CD4(+) T lymphocytes. However, only CD4(+) Th2 and Th0, but not Th1, CD4(+) T-cell clones have been reported to efficiently support HIV-1 replication. This dichotomous pattern was further investigated in the present study in Th1, Th2, or Th0 cell lines derived from umbilical human cord blood and in T-cell clones obtained from the peripheral blood mononuclear cells (PBMC) of healthy adults. Both primary and laboratory-adapted HIV-1 strains with CCR5 as the exclusive entry coreceptor (R5 viruses) efficiently replicated in Th1, Th2, and Th0 cells. In sharp contrast, CXCR4-dependent (X4) viruses poorly replicated in both polarized and unpolarized CD4(+) T cells, including adults' PBMC infected several days after mitogenic stimulation. Unlike the X4 HIV-1(NL4-3), a chimera in which the env gene had been replaced with that of the R5 HIV-1(NL(AD8)), efficiently replicated in both Th1 and Th2 cells. This X4-dependent restriction of HIV replication was not explained by either the absence of functional CXCR4 on the cell surface or by the inefficient viral entry and reverse transcription. T-cell receptor stimulation by anti-CD3 monoclonal antibodies fully rescued X4 HIV-1 replication in both Th1 and Th2 cells, whereas it did not alter the extent and kinetics of R5 HIV-1 spreading. Thus, R5 HIVs show a replicative advantage in comparison to X4 viruses in their ability to efficiently propagate among suboptimally activated T lymphocytes, regardless of their polarized or unpolarized functional profiles. This observation may help to explain the absolute predominance of R5 HIVs over X4 viruses observed after viral transmission and during early-stage disease.

Adult↗

PubMed2005

Chronic alcohol consumption results in higher simian immunodeficiency virus replication in mucosally inoculated rhesus macaques.

The influence of alcohol consumption on HIV pathogenesis is not well understood. In this study we used the simian immunodeficiency virus (SIV)/macaque model of HIV infection to study the influence of chronic binge alcohol consumption on SIV infection. Rhesus macaques were fed alcohol or isocaloric amounts of sucrose via indwelling intragastric catheters and then inoculated with SIVmac251 by the rectal route. Real-time RT-PCR for SIV gag mRNA showed significantly higher plasma viral copies in alcohol-consuming macaques at 4 and 6 weeks pi, compared with sucrose controls. The viral copies were 1 to 2 logs higher in these animals. The percentage of CD8+ lymphocytes in the duodenum of alcohol-consuming macaques was significantly lower than in sucrose-consuming macaques both before infection as well as at different time points postinfection. Also, the percentage of CD4(+)CD3+ lymphocytes in the intestines was significantly higher in alcohol-consuming macaques before infection. These findings suggest that a higher percentage of SIV target cells (CD4) in the gut coupled with lower percentages of CD8 cells, which could be important in controlling virus replication, may be responsible for the higher SIV loads observed in alcohol-consuming macaques.

Administration, Rectal↗

PubMed1997

Low-dose oral type I interferons reduce early virus replication of murine cytomegalovirus in vivo.

Immunity to viral infections involves both innate and antigen-specific immune responses. The antiviral properties of interferons (IFNs) are part of the innate immune response. Low doses of type I IFNs (IFN-alpha and IFN-beta) administered daily (10 IU per mouse) by the oral route significantly reduced the early replication of murine cytomegalovirus (MCMV) in both the spleen and liver of MCMV-infected susceptible BALB/c mice. Significant inhibition of virus replication was observed for two different inoculum doses of virus (2 x 10(4) pfu per mouse [0.6 LD50] and 2 x 10(4.12) pfu per mouse [0.8 LD50]). Analysis of IFN retention, using [35S]-labeled IFN-alpha1 compared with the nonreceptor binding mutant IFN-alpha1 (R33M) administered orally to mice, revealed binding of wild-type IFN-alpha1 to several tissues. In particular, IFN was retained by tissues proximal to lymphoid regions, including the posterior nasal cavity, posterior tongue, small intestine, and rectum. These findings suggest that type I IFNs may inhibit MCMV replication by distal binding of the orally administered IFN to various tissues, which in turn augment the primary immune response to virus infection.

Administration, Oral↗

PubMed1994

Multiple functions of capsid protein phosphorylation in duck hepatitis B virus replication.

We have investigated the role of phosphorylation of the capsid protein of the avian hepadnavirus duck hepatitis B virus in viral replication. We found previously that three serines and one threonine in the C-terminal 24 amino acids of the capsid protein serve as phosphorylation sites and that the pattern of phosphorylation at these sites in intracellular viral capsids is complex. In this study, we present evidence that the phosphorylation state of three of these residues affects distinct steps in viral replication. By substituting these residues with alanine in order to mimic serine, or with aspartic acid in order to mimic phosphoserine, and assaying the effects of these substitutions on various steps in virus replication, we were able to make the following inferences. (i) The presence of phosphoserines at residues 245 and 259 stimulates DNA synthesis within viral nucleocapsids. (ii) The absence of phosphoserine at residue 257 and at residues 257 and 259 stimulates covalently closed circular DNA synthesis and virus production, respectively. (iii) The presence of phosphoserine at position 259 is required for initiation of infection. The results implied that both phosphorylated and nonphosphorylated capsid proteins were necessary for a nucleocapsid particle to carry out all its functions in virus replication, explaining why differential phosphorylation of the capsid protein occurs in hepadnaviruses. Whether these differentially phosphorylated proteins coexist on the same nucleocapsid, or whether the nucleocapsid acquires sequential functions through selective phosphorylation and dephosphorylation, is discussed.

Alanine↗