Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Virus Replication”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2003

Conserved cysteine and histidine residues in the putative zinc finger motif of the influenza A virus M1 protein are not critical for influenza virus replication.

The influenza virus matrix protein (M1) possesses a cysteine and histidine (CCHH) motif in the helix 9 (H9) and adjacent region ((148)CATCEQIADSQHRSH(162)). The CCHH motif has been proposed as a putative zinc finger motif and zinc-binding activity has been implicated in virus uncoating as well as transcription inhibition and mRNA regulation. The function of the CCHH motif in the influenza virus life cycle was investigated by site-directed mutagenesis (alanine replacement) and by rescuing mutant viruses by reverse genetics. Mutant viruses containing an alanine replacement of the cysteine and histidine residues, either individually or in combination, were seen to exhibit wt phenotype in multiple virus growth cycles and plaque morphology. In addition, synthetic peptides containing the putative zinc finger motif did not inhibit virus replication in MDCK cells. However, mutation of Ala(155) in H9 was lethal for rescuing infectious virus. These data show that the CCHH motif does not provide a critical function in the influenza virus life cycle in cell culture and that the zinc-binding function may not be involved in virus biology. However, the lethal phenotype of the Ala(155) mutation shows that the H9 region of M1 provides some other critical function(s) in virus replication.

Amino Acid Motifs↗
PubMed1995

Th1 cells specific for HIV-1 gag p24 are less efficient than Th0 cells in supporting HIV replication, and inhibit virus replication in Th0 cells.

This report provides three lines of evidence to suggest that T-helper type 1 (Th1) and type 0 (Th0) cells could play an opposing role in acquired immune deficiency syndrome (AIDS). Using a panel of Th1 and Th0 clones specific for human immunodeficiency virus-1 (HIV-1) gag p24, derived from seronegative volunteers immunized with gag p24: Ty virus-like particles, a Th1 clone specific for tuberculin (PPD), and a Th0 clone derived by random activation from the same volunteer, we have demonstrated the following differences in the capacity of these clones to regulate the in vitro replication of HIV. (1) Th1 clones were less efficient than Th0 clones in supporting HIV replication, both in their resting state (by 10-1000-fold) and after antigen activation (by five to 100-fold). Furthermore, the infectious titre of HIV recovered from the Th0 population was more than 1000-fold higher than virus from the Th1 population, and the number of HIV-infected Th0 cells was five to 16 times higher than the number of infected Th1 cells. (2) Antigen- or mitogen-activated Th1, but not Th0 clones, inhibited HIV in bystander CEM-4 cells. Th1 cells also inhibited HIV in autologous and allogeneic Th0 cells. The level of inhibition in these experiments ranged from 50% to 100% and was three to 10-fold higher and more sustained in the presence of p24-specific clones compared to the PPD-specific Th1 clone. The capacity of Th1 cells to inhibit HIV in neighbouring cells was also reflected in the reduced replication of HIV in the clones immediately after antigen activation compared to unstimulated cells. Kinetic studies of virus production, cytokine release and proliferation showed that inhibition of HIV was associated with peak cytokine release and preceeded proliferation. (3) The Th1 clones had higher cytolytic potential than the Th0 clones. Therefore, the HIV inhibitory activity of Th1 cells could be partly due to cell to cell killing. These data demonstrate the opposing effects of Th1 and Th0 cells on the in vitro replication of HIV, and suggest that Th1 cells might be important in immunity whereas Th0/Th2 cells might lay a role in promoting disease.

CD4-Positive T-Lymphocytes↗
PubMed2002

Correlations between lung proinflammatory cytokine levels, virus replication, and disease after swine influenza virus challenge of vaccination-immune pigs.

During experimental infection of pigs with swine influenza virus (SIV), there is a strong temporal correlation between peak virus titers in the lungs, levels of different proinflammatory cytokines in bronchoalveolar lavage (BAL) fluids, and disease. Vaccination against SIV can greatly reduce or prevent virus replication after challenge and the resulting disease. Here, we took advantage of pigs from vaccination-challenge experiments, with different degrees of virological and clinical protection, to further correlate SIV replication with cytokines and disease. Forty-nine pigs were vaccinated twice with a commercial inactivated SIV vaccine or with experimental vaccines, and 35 control pigs were not vaccinated. Between 2 and 4 weeks after the last vaccination, all pigs were challenged intratracheally with SIV. Twenty-four hours after the challenge, we determined body temperatures, respiratory scores, lung virus titers, and neutrophils and cytokines in BAL fluids. Interferon-alpha (IFN-alpha), tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1), and -6 (IL-6) were determined by bioassay, and IL-8 by a commercial ELISA. The results were analyzed for three comparison groups. The unvaccinated control pigs (group 1, n = 35) were positive for all or most parameters examined. Vaccinated pigs with challenge virus replication in the lungs (group 2, n = 28) had slightly lower virus titers than the challenge control pigs, and clear reductions in disease severity and mean titers of all five cytokines, but neutrophil numbers were not affected. Vaccinated pigs without detectable virus replication (group 3, n = 21) were largely protected against clinical signs and neutrophil infiltration. Mean levels of IFN-alpha, TNF-alpha, and IL-6, but not IL-1 or IL-8, were lower than in both other groups. Virus titers in the lungs of individual pigs showed highly significant correlations with IFN-alpha and IL-6, and lower correlations with TNF-alpha and IL-8. Clinical signs were most closely associated with IFN-alpha, IL-6, and TNF-alpha. The relationship between disease and IL-8 or IL-1 was much weaker. Our data provide further evidence for a role of IFN-alpha, TNF-alpha, and IL-6 in the pathogenesis of SIV. The similarities with cytokine profiles during human influenza virus infection are discussed.

Animals↗
PubMed2001

The bet gene of feline foamy virus is required for virus replication.

Foamy viruses (FV) are complex retroviruses with additional bel genes located between env and the 3' long-terminal repeat. The functions of the bel 2 and bet genes are unknown and both are dispensable for replication of the prototypic human foamy virus in cell cultures. We examined the function(s) of bel 2 and bet of the distantly related feline foamy virus (FFV) in the proviral context. Mutagenesis was used to alter the Bel 2 and Bet or to abrogate their expression. The Bel 2/Bet mutants showed a 1000-fold reduced viral titer in feline kidney cells; in human 293T cells, viral titer was only about 10-fold reduced compared to wild-type FFV. In both cell types, the Bel 2/Bet mutations resulted in a reduced release of FFV particles. The results indicate that FFV Bet is required for efficient virus replication. The functions of the Bel 2 and Bet proteins are discussed.

Amino Acid Sequence↗
PubMed1995

Long-term follow-up of hepatitis B virus and hepatitis C virus replicative levels in chronic hepatitis patients coinfected with both viruses.

Dual infection with hepatitis B and C viruses is often encountered in endemic areas of both viruses. However, understanding of the clinical and virological implications is limited. The aim of this study was to investigate the role of each virus in liver injury and the interaction between the two viruses in dual infection with hepatitis B and C viruses. Three patients who had chronic infection with both hepatitis B and C viruses were examined, and a longitudinal study of both serum hepatitis B virus DNA and hepatitis C virus RNA levels over 4 years was undertaken. The results were correlated with serum alanine aminotransferase levels. Serum alanine aminotransferase values showed a relationship with hepatitis B virus replicative levels, but not with hepatitis C virus replicative levels in all 3 patients. Serial changes of replicative levels of both viruses were studied, and it was found that hepatitis C virus replicative levels were enhanced after the decline of hepatitis B virus replication in 1 of the 3 patients. In the remaining 2 patients, a transient rise of hepatitis C virus replicative levels in association with a decrease of hepatitis B virus replication was also observed during part of the follow-up period. These findings indicate that hepatitis B virus may play a dominant etiological role in liver injury, and that a suppressive action between hepatitis B and C viruses may occur in dual infection with both viruses.

Adult↗
PubMed1998

Rubella virus replication complexes are virus-modified lysosomes.

Replication complexes are membrane-bound cytoplasmic vacuoles involved in rubella virus (RV) replication. These structures can be identified by their characteristic morphology at the electron microscopy (EM) level and by their association with double-stranded (ds) RNA in immunogold labeling EM studies. Although these virus-induced structures bear some resemblance to lysosomes, their exact nature and origin are unknown. In this study, the localization of two lysosomal markers, lysosomal-associated membrane protein (Lamp-1) and acid phosphatase, relative to the replication complexes was examined by light and electron microscopy. Confocal microscopy using antibodies to dsRNA and Lamp-1 showed colocalization of these two markers in the cytoplasm of RV-infected cells. Immunogold labeling EM studies using antibodies to Lamp-1 confirmed that Lamp-1 was associated with RV replication complexes. EM histochemical studies demonstrated the presence of acid phosphatase in the vacuoles of RV replication complexes. Taken together, these studies show that RV replication complexes are virus-modified lysosomes.

Acid Phosphatase↗
PubMed1983

Virus replication and liver disease in chronic hepatitis B virus infection.

Recent studies on the natural history of chronic hepatitis B virus infection have provided evidence for a close temporal relationship between the phase of active virus replication and development of liver lesions. To assess the role that virus replication plays in this phase in determining the severity of the liver disease, we studied serum levels of virus-specific DNA-polymerase activity and hepatitis Be antigen/antibody status in 48 chronic carriers of the hepatitis B surface antigen found positive for the hepatitis B core antigen in the liver. There was a remarkably evident inverse correlation between virus replication activity and liver disease activity, patients with minimal histological changes having the highest DNA-polymerase levels (mean +/- SD: 3879 +/- 2557 cpm) and those with severe chronic active hepatitis the lowest enzyme levels (419 +/- 246 cpm), while cases of chronic persistent hepatitis and of mild chronic active hepatitis had intermediate levels. Serum hepatitis Be antigen was detected in 31/32 patients with milder liver lesions and in 11/16 with severe liver lesions; the remaining five cases were anti-HBe-positive despite the presence of the core antigen in the liver. Serum levels of virus replication markers closely correlated with the distribution pattern of the core antigen in the liver. These findings indicate that in chronic hepatitis B the severity of liver disease is not directly related to levels of virus replication, thus suggesting a predominant role of host immune mechanisms.

Carrier State↗
PubMed2004

Innate cellular response to virus particle entry requires IRF3 but not virus replication.

Mammalian cells respond to virus infections by eliciting both innate and adaptive immune responses. One of the most effective innate antiviral responses is the production of alpha/beta interferon and the subsequent induction of interferon-stimulated genes (ISGs), whose products collectively limit virus replication and spread. Following viral infection, interferon is produced in a biphasic fashion that involves a number of transcription factors, including the interferon regulatory factors (IRFs) 1, 3, 7, and 9. In addition, virus infection has been shown to directly induce ISGs in the absence of prior interferon production through the activation of IRF3. This process is believed to require virus replication and results in IRF3 hyperphosphorylation, nuclear localization, and proteasome-mediated degradation. Previously, we and others demonstrated that herpes simplex virus type 1 (HSV-1) induces ISGs and an antiviral response in fibroblasts in the absence of both interferon production and virus replication. In this report, we show that the entry of enveloped virus particles from diverse virus families elicits a similar innate response. This process requires IRF3, but not IRF1, IRF7, or IRF9. Following virus replication, the large DNA viruses HSV-1 and vaccinia virus effectively inhibit ISG mRNA accumulation, whereas the small RNA viruses Newcastle disease virus, Sendai virus, and vesicular stomatitis virus do not. In addition, we found that IRF3 hyperphosphorylation and degradation do not correlate with ISG and antiviral state induction but instead serve as a hallmark of productive virus replication, particularly following a high-multiplicity infection. Collectively, these data suggest that virus entry triggers an innate antiviral response mediated by IRF3 and that subsequent virus replication results in posttranslational modification of IRF3, such as hyperphosphorylation, depending on the nature of the incoming virus.

Animals↗
PubMed2003

Lymphoid tissue tropism of porcine reproductive and respiratory syndrome virus replication during persistent infection of pigs originally exposed to virus in utero.

The ability of porcine reproductive and respiratory syndrome virus (PRRSV) to establish a persistent infection is the principal contributing factor to the world-wide spread of the disease. Several studies have documented the course of viral infection in postnatally infected pigs; however, very little is known regarding sites of virus replication during persistent infection of pigs exposed to PRRSV in utero. In this study, virus replication and PRRSV-specific antibody were followed for several hundred days in a group of pigs derived from three sows infected at 90 days of gestation with PRRSV isolate VR-2332. Eighty-four percent of pigs were born viremic with a mortality of 54% within 21 days after birth. At approximately 60 days sera from pigs were negative for virus by virus isolation. Analysis of virus replication in the tissues of pigs randomly sacrificed between 63 and 132 days showed no evidence of virus in lung and other non-lymphoid organs. However, virus was easily recovered from tonsil and lymph nodes and in situ hybridization identified these tissues as sites of virus replication. Even though replication was at a low level, virus was easily transmitted to sentinel pigs. By 260 days pigs became seronegative and did not transmit virus to sentinel pigs. Sacrifice of remaining pigs after 300 days showed no evidence of virus in blood and tissues. This study shows that congenital PRRSV-infected pigs can support virus replication for an extended period during which virus replication is primarily restricted to tonsil and lymph nodes.

Animals↗
PubMed2002

Rapid directional translocations in virus replication.

By viewing virus development in real time, the experiments reported here reveal novel processes--rapid directional translocations--that are likely to be important elements of virus replication. Herpes simplex virus type 1 (HSV-1) was labeled by the fusion of the green fluorescent protein to a structural protein of its tegument (VP11/12), the product of gene UL46. Infection of cultured cells with this recombinant virus (GHSV-UL46) produced fluorescent particles that were distributed throughout the cytoplasm with concentrations in the perinuclear region; they were absent from the nucleus. Viewing infected cells in real time by means of video microscopy produced a novel dynamic picture of virus development. Most strikingly, some of the fluorescent particles exhibited extremely rapid directional translocations at velocities as great as 5 microm/s. The trajectories and destinations of these particles suggest that the rapid directional translocations serve at least three functions: the rapid transport of viral components to and between cytoplasmic processing stations, the delivery of materials for functions specific to the perinuclear region, and the conveyance of maturing virus particles to the plasma membrane. These rapid directional translocations are novel elements of virus assembly that are likely to be critical for efficient replication.

Animals↗
PubMed2002

The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication.

All viruses with negative-sense RNA genomes encode a single-strand RNA-binding nucleoprotein (NP). The primary function of NP is to encapsidate the virus genome for the purposes of RNA transcription, replication and packaging. The purpose of this review is to illustrate using the influenza virus NP as a well-studied example that the molecule is much more than a structural RNA-binding protein, but also functions as a key adapter molecule between virus and host cell processes. It does so through the ability to interact with a wide variety of viral and cellular macromolecules, including RNA, itself, two subunits of the viral RNA-dependent RNA polymerase and the viral matrix protein. NP also interacts with cellular polypeptides, including actin, components of the nuclear import and export apparatus and a nuclear RNA helicase. The evidence for the existence of each of these activities and their possible roles in transcription, replication and intracellular trafficking of the virus genome is considered.

Actins↗
PubMed1995

Suppression of simian immunodeficiency virus replication by human immunodeficiency virus type 1 trans-dominant negative rev mutants.

We demonstrate that trans-dominant negative rev mutants are able to suppress simian immunodeficiency virus provirus replication in both transient cotransfection assays and stably transduced HUT 78 cells. These studies suggest that the efficacy of trans-dominant rev strategies in reducing viral burden may be evaluated in a simian immunodeficiency virus-rhesus macaque animal model.

Amino Acid Sequence↗
PubMed1998

Inhibition of apoptosis and virus replication in feline immunodeficiency virus-infected cells by N-acetylcysteine and ascorbic acid.

Infection of feline immunodeficiency virus (FIV) has been shown to induce apoptosis that might be associated with the lymphocyte depletion in the infected cats. To investigate the inhibitory effect of antioxidants on FIV-induced apoptosis, we examined the effect of N-acetylcysteine (NAC) and ascorbic acid (AA) on apoptosis and virus replication in feline lymphoblastoid (Fel-039) and fibroblastoid (CRFK) cell lines infected with FIV. The treatment with NAC or AA induced a significant inhibition of viral replication and apoptosis in Fel-039 cells and tumor necrosis factor alpha (TNF-alpha)-treated CRFK cells infected with FIV. Both cell lines in the presence of noncytotoxic concentrations of NAC or AA showed in increase of intracellular glutathione (GSH) level, which might protect the cells against oxidative stresses exerted by FIV infection and TNF-alpha treatment. On the basis of these in vitro results, we suggest that antioxidant therapies aimed at restoring depleted GSH level might be effective for inhibition of viral replication and cell death associated with the development of immunodeficiency.

Acetylcysteine↗
PubMed1998

Binding of a cellular factor to the 3' untranslated region of the RNA genomes of entero- and rhinoviruses plays a role in virus replication.

The presence of cellular factors that bind to the 3' untranslated region (UTR) of picornaviruses was investigated by electrophoretic mobility shift assays (EMSAs). A cellular factor(s) that binds specifically the 3' UTR of polio-, coxsackie- and rhinoviruses was detected. Furthermore, this factor(s) is distinct from those which bind to the 5' terminal 88 nt (the 'cloverleaf') of poliovirus. Mutations within the 3' UTR which decrease the affinity of the RNA for the cellular factor in EMSAs decrease RNA replication and virus viability. Revertants of these mutants display changes which are predicted to stabilize the RNA secondary structure of the 3' UTR. These results indicate that binding of a cellular factor to the UTR plays a role in virus replication and that RNA secondary structure is important for this function.

Base Sequence↗
PubMed2002

Herpes simplex virus ICP0 and ICP34.5 counteract distinct interferon-induced barriers to virus replication.

Interferon inhibits virus replication through multiple mechanisms. Here we show that herpes simplex virus proteins ICP0 and ICP34.5 overcome interferon-induced barriers to viral transcription and translation, respectively. These cytokine-induced antiviral mechanisms are differentially expressed in established cell lines: U2OS cells do not mount the IFN-induced mechanism targeted by ICP0, and Vero cells may be defective for the mechanism targeted by ICP34.5.

Animals↗
PubMed2000

Mutational analysis of the rubella virus nonstructural polyprotein and its cleavage products in virus replication and RNA synthesis.

Rubella virus nonstructural proteins, translated from input genomic RNA as a p200 polyprotein and subsequently processed into p150 and p90 by an intrinsic papain-like thiol protease, are responsible for virus replication. To examine the effect of p200 processing on virus replication and to study the roles of nonstructural proteins in viral RNA synthesis, we introduced into a rubella virus infectious cDNA clone a panel of mutations that had variable defective effects on p200 processing. The virus yield and viral RNA synthesis of these mutants were examined. Mutations that completely abolished (C1152S and G1301S) or largely abolished (G1301A) cleavage of p200 resulted in noninfectious virus. Mutations that partially impaired cleavage of p200 (R1299A and G1300A) decreased virus replication. An RNase protection assay revealed that all of the mutants synthesized negative-strand RNA as efficiently as the wild type does but produced lower levels of positive-strand RNA. Our results demonstrated that processing of rubella virus nonstructural protein is crucial for virus replication and that uncleaved p200 could function in negative-strand RNA synthesis, whereas the cleavage products p150 and p90 are required for efficient positive-strand RNA synthesis.

Animals↗
PubMed1976

Inhibition of pseudorabies virus replication by vesicular stomatitis virus. II Activity of defective interfering particles.

Purified defective interfering (DI) particles of vesicular stomatitis virus (VSV) inhibit the replication of a heterologous virus, pseudorabies virus (PSR), in hamster (BHK-21) and rabbit (RC-60) cell lines. In contrast to infectious B particles of VSV, UV irradiation of DI particles does not reduce their ability to inhibit PSR replication. However, UV irradiation progressively reduces the ability of DI particles to cause homologous interference with B particle replication. Pretreatment with interferon does not affect the ability of DI particles to inhibit PSR replication in a rabbit cell line (RC-60) in which RNA, but not DNA, viruses are sensitive to the action of interferon. Under similar conditions of interferon pretreatment, the inhibition of PSR by B particles is blocked. These data suggest that de novo VSV RNA or protein synthesis is not required for the inhibition of PSR replication by DI particles. DI particles that inhibit PSR replication also inhibit host RNA and protein synthesis in BHK-21 and RC-60 cells. Based on the results described and data in the literature, it is proposed that the same component of VSV B and DI particles is responsible for most, if not all, of the inhibitory activities of VSV, except homologous interference.

Cell Line↗