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Results for “viral replication”

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At least 109 records · Page 6Linked to original sources

PubMed2005

RSV-induced prostaglandin E2 production occurs via cPLA2 activation: role in viral replication.

Prostaglandins (PGs) are lipid mediators that participate in the regulation of immunological and inflammatory responses, and PG production can affect viral replication. In this study, we have investigated the mechanism of PGE2 production in airway epithelial cells, following respiratory syncytial virus (RSV) infection, and its role in viral replication. We show that RSV infection strongly induces PGE2 secretion, in a time- and replication-dependent manner, through increased cyclooxygenase-2 (COX-2) expression, which occurs independently from viral or cellular protein synthesis. RSV infection induces arachidonic acid release through induction of cytoplasmic phospholipase A2 (cPLA2) enzymatic activity and its membrane translocation. Specific inhibitors of cPLA2 significantly block RSV-induced PGE2 secretion, indicating a key role of cPLA2 in viral-induced PG production. Blocking PG secretion, through cPLA2 or COX-2 inhibition, results in impairment of RSV replication and subsequent RSV-mediated epithelial cell responses, suggesting that inhibition of PG secretion could be beneficial in RSV infection by reducing proinflammatory mediator production.

Arachidonic Acid↗

PubMed2002

Discordance between frequency of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon-producing CD4(+) T cells and HIV-1-specific lymphoproliferation in HIV-1-infected subjects with active viral replication.

One hallmark of uncontrolled, chronic human immunodeficiency virus type 1 (HIV-1) infection is the absence of strong HIV-1-specific, CD4(+) T-cell-proliferative responses, yet the mechanism underlying this T helper (Th)-cell defect remains controversial. To better understand the impact of HIV-1 replication on Th-cell function, we compared the frequency of CD4(+) Th-cell responses based on production of gamma interferon to lymphoproliferative responses directed against HIV-1 proteins in HIV-1-infected subjects with active in vivo viral replication versus those on suppressed highly active antiretroviral therapy (HAART). No statistically significant differences in the frequencies of cytokine-secreting, HIV-1-specific CD4(+) T cells between the donor groups were found, despite differences in viral load and treatment status. However, HIV-1-specific lymphoproliferative responses were significantly greater in the subjects with HAART suppression than in subjects with active viral replication. Similar levels of HIV-1 RNA were measured in T-cell cultures stimulated with HIV-1 antigens regardless of donor in vivo viral loads, but only HIV-1-specific CD4(+) T cells from subjects with HAART suppression proliferated in vitro, suggesting that HIV-1 replication in vitro does not preclude HIV-1-specific lymphoproliferation. This study demonstrates a discordance between the frequency and proliferative capacity of HIV-1-specific CD4(+) T cells in subjects with ongoing in vivo viral replication and suggests that in vivo HIV-1 replication contributes to the observed defect in HIV-1-specific CD4(+) T-cell proliferation.

Adult↗

PubMed2000

Targeting of the gene product encoded by ORF UL56 of human cytomegalovirus into viral replication centers.

The highly conserved DNA-binding protein pUL56 of human cytomegalovirus (HCMV) was found to be predominantly localized throughout the nucleus as well as in viral replication centers of infected cells. The latter localization was abolished by phosphono acetic acid, an inhibitor of viral DNA replication. Immunofluorescence revealed that pUL56 co-localized in replication centers alongside pUL112-113 and pUL44 at late times of infection. By co-immunoprecipitations, a direct interaction with pUL44, a protein of the replication fork, was detected. These results showed for the first time that HCMV pUL56 is localized in viral replication centers, implicating that DNA replication is coupled with packaging.

Animals↗

PubMed1989

[Viral replication, histologic damage and enzymatic activity in chronic hepatopathies caused by B virus].

The future of patients with chronic hepatitis (HC) due to B virus depends above all on the tendency of the interaction between viral activity and immune response. Viral activity (replication) (RV) can be expressed in these patients by two variants: a) "complete" or "early", associated with the presence in serum of HBsAg, HBeAg, and significant DNA polymerase activity, and b) "incomplete" or "late", in which anti-HBe is found in serum and there are scant or no histopathologic changes ("healthy carriers" in some cases). In prolonged infections viral replication declines gradually, although viral capsid protein continues to be synthesized and DNA-HBV is integrated into the genome. Viral replication per se does not condition the histologic damage (DH) expressive of liver cirrhosis with HBV (HCB). Other publications take a different view of this problem. The increase in viral replication often is proportional to a rise in serum GPT (an expression of histologic damage), but viral replication is not always associated with a progressive disease course. The immune defense leads to cytolysis and subsequent elimination of the HB virus. Some patients with high HBsAg levels have little active forms of liver cirrhosis; the DNA-HBV integrated would be capable of producing HBsAg but not HBcAg. It is precisely this that induces the response of cytotoxic T lymphocytes at the level of the hepatocyte surface. The presence in serum of anti-HBe IgM would be related to the expression of HBcAg on the hepatocyte membrane and/or the liberation of HBcAg particles by lysed hepatocytes. The relationship between the degree of histologic damage and serum aminotransferase levels is better established.

Chronic Disease↗

PubMed2005

Stage-specific effects of Plasmodium falciparum-derived hemozoin on blood mononuclear cell TNF-alpha regulation and viral replication.

BACKGROUND: The molecular immunological interactions between HIV and malaria are largely undefined. Since tumor necrosis factor (TNF)-alpha is elevated during acute malaria and increases with HIV-1 disease progression, TNF-alpha production may be an important mediator for interactions between malaria and HIV-1. METHODS: To examine the stage-specific immunological interactions between HIV and malaria, peripheral blood mononuclear cells (PBMC) and CD14 cells were isolated and cultured from rhesus macaques at different stages of SIV infection. Cultures were stimulated with lipopolysaccharide (LPS) and interferon (IFN)-gamma in the presence of Plasmodium falciparum-derived hemozoin (Hz) or synthetic Hz (sHz). TNF-alpha transcripts and soluble protein were examined by real time reverse transcription-PCR and ELISA, respectively. The effects of Hz on viral replication were determined by measurement of p27 antigen with varying concentrations of TNF-alpha neutralizing antibodies. RESULTS: Hz and sHz significantly increased LPS- and IFN-gamma-induced TNF-alpha protein and transcripts in PBMC from animals with late stage SIV infection (i.e., AIDS). Hz and sHz also induced high levels of sustained TNF-alpha transcripts in PBMC from the AIDS group. During the late stage of disease, CD14 cells were the primary source of TNF-alpha production. Stimulation of PBMC with Hz and sHz significantly increased viral replication that was dose-dependently reduced by the addition of TNF-alpha neutralizing antibodies. CONCLUSIONS: Hz promotes high levels of TNF-alpha production from PBMC during AIDS and increases viral replication in SIV-infected animals.

Animals↗

PubMed2004

Role of accessory proteins of HTLV-1 in viral replication, T cell activation, and cellular gene expression.

Human T-cell lymphotropic virus type 1 (HTLV-1), causes adult T cell leukemia/lymphoma (ATLL), and initiates a variety of immune mediated disorders. The viral genome encodes common structural and enzymatic proteins characteristic of all retroviruses and utilizes alternative splicing and alternate codon usage to make several regulatory and accessory proteins encoded in the pX region (pX ORF I to IV). Recent studies indicate that the accessory proteins p12I, p27I, p13II, and p30II, encoded by pX ORF I and II, contribute to viral replication and the ability of the virus to maintain typical in vivo expression levels. Proviral clones that are mutated in either pX ORF I or II, while fully competent in cell culture, are severely limited in their replicative capacity in a rabbit model. These HTLV-1 accessory proteins are critical for establishment of viral infectivity, enhance T-lymphocyte activation and potentially alter gene transcription and mitochondrial function. HTLV-1 pX ORF I expression is critical to the viral infectivity in resting primary lymphocytes suggesting a role for the calcineurin-binding protein p12I in lymphocyte activation. The endoplasmic reticulum and cis-Golgi localizing p12I activates NFAT, a key T cell transcription factor, through calcium-mediated signaling pathways and may lower the threshold of lymphocyte activation via the JAK/STAT pathway. In contrast p30II localizes to the nucleus and represses viral promoter activity, but may regulate cellular gene expression through p300/CBP or related co-activators of transcription. The mitochondrial localizing p13II induces morphologic changes in the organelle and may influence energy metabolism infected cells. Future studies of the molecular details HTLV-1 "accessory" proteins interactions will provide important new directions for investigations of HTLV-1 and related viruses associated with lymphoproliferative diseases. Thus, the accessory proteins of HTLV-1, once thought to be dispensable for viral replication, have proven to be directly involved in viral spread in vivo and represent potential targets for therapeutic intervention against HTLV-1 infection and disease.

Alternative Splicing↗

PubMedDate not supplied

Recurrent herpes simplex labialis: viral replication and clinical course.

The purpose of this study was to provide additional information on the clinical course and viral replication kinetics of herpes simplex virus (HSV) in recurrent herpes labialis. Data were obtained on 20 subjects who were followed for five days from the first day of the lesion. HSV was isolated in 17 subjects (85%); 75% were positive on day 1 of the lesion. Median HSV titer on day 1 was 1.7 x 10(3)/0.2ml. Isolation rates and titers dropped sharply and virus could no longer be detected by day 4. The clinical course both in terms of the frequency and the severity of the symptoms paralleled the kinetics of viral replication. Thermography delineated location of subsequent lesions in three early symptomatic patients who were studied at the time when no visible lesions were observed. These data are felt to provide useful background information for future studies on the efficacy of topical antiviral agents.

Adolescent↗

PubMed2005

Neuronal activity regulates viral replication of herpes simplex virus type 1 in the nervous system.

Herpes simplex virus types 1 and 2 (HSV-1, -2) infect and also establish latency in neurons. In the present study, the authors investigated the influence of neuronal activity on the replication of HSV-1. The results showed that the sodium channel blocker tetrodotoxin (TTX) and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) could significantly increase viral replication in primary neuronal cultures, by two- to fourfold. In contrast, KCl reduced viral production by at least 80% in the same cultures. Inhibitors of GABA(A) receptors completely abolished the effects of GABA. Intravitreously injected TTX in a mouse corneal scarification model enhanced the viral titers > 10-fold in both the trigeminal ganglia and the brain. At 2 h post infection, both TTX and GABA significantly up-regulated the levels of transcription for the viral immediate early (IE) genes ICP0, ICP4, and ICP27, as revealed by real time PCR. These results indicate that the neuronal excitation status may dictate the efficiency of HSV-1 viral replication, probably by regulating the levels of viral IE gene expression. These are the first findings connecting neuronal activity to the molecular mechanisms of HSV replication in the nervous system, which may significantly influence our view of herpesvirus infection and latency.

Animals↗

PubMed1994

RNA polymerase II is aberrantly phosphorylated and localized to viral replication compartments following herpes simplex virus infection.

During lytic infection, herpes simplex virus subverts the host cell RNA polymerase II transcription machinery to efficiently express its own genome while repressing the expression of most cellular genes. The mechanism by which RNA polymerase II is directed to the viral delayed-early and late genes is still unresolved. We report here that RNA polymerase II is preferentially localized to viral replication compartments early after infection with herpes simplex virus type 1. Concurrent with recruitment of RNA polymerase II into viral compartments is a rapid and aberrant phosphorylation of the large subunit carboxy-terminal domain (CTD). Aberrant phosphorylation of the CTD requires early viral gene expression but is not dependent on viral DNA replication or on the formation of viral replication compartments. Localization of RNA polymerase II and modifications to the CTD may be instrumental in favoring transcription of viral genes and repressing specific transcription of cellular genes.

Animals↗

PubMed1995

Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes and enhances viral replication in HIV-infected monocytic cells.

Monocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time. Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro. The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B (p50/p65), which binds to a specific sequence in the HIV-long terminal repeat. The present study demonstrates that triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in HIV-infected human monocytic cells. Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti-CR1 or anti-CR3 Abs or with C3 fragments. Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS. We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50/p65 in infected cells. Translocation of NF-kappa B p50/p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors. The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha. TNF-alpha did not mediate the translocation of NF-kappa B p50/p65 induced by triggering of complement receptors. Taken together, these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor-mediated nuclear translocation of the NF-kappa B complex.

Biological Transport↗

PubMed2005

Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication.

Hepatitis C virus (HCV) is a positive-strand RNA virus that frequently causes persistent infection associated with severe liver disease. HCV nonstructural protein 5A (NS5A) is essential for viral replication. Here, the kinase Raf-1 was identified as a novel cellular binding partner of NS5A, binding to the C-terminal domain of NS5A. Raf-1 colocalizes with NS5A in the HCV replication complex. The interaction of NS5A with Raf-1 results in increased Raf-1 phosphorylation at serine 338. Integrity of Raf-1 is crucial for HCV replication: inhibition of Raf-1 by the small-molecule inhibitor BAY43-9006 or downregulation of Raf-1 by siRNA attenuates viral replication.

Animals↗

PubMedDate not supplied

Analysis of liver disease, nuclear HBcAg, viral replication, and hepatitis B virus DNA in liver and serum of HBeAg Vs. anti-HBe positive carriers of hepatitis B virus.

Nine HBeAg+ and 24 anti-HBe+ subjects with chronic hepatitis B virus (HBV) infection were studied for HBV DNA in the serum by molecular hybridization, for HBcAg in the liver by immunofluorescence, and for histologic evidence of liver disease. All HBeAg+ patients had underlying chronic liver disease (chronic persistent hepatitis, chronic active hepatitis, or cirrhosis with or without hepatocellular carcinoma), and all were found positive for both HBV DNA in the serum and HBcAg in the nucleus of hepatocytes. Of the 24 anti-HBe+ individuals, 18 had various forms of chronic liver disease. Six HBsAg+/anti-HBe+ patients had normal liver histology except for numerous "ground-glass" hepatocytes with abundant cytoplasmic HBsAg. All six were negative for nuclear HBcAg and serum HBV DNA, but three showed HBV DNA which appeared to be integrated into unique sites in host liver DNA by hybridization analysis. In contrast, 14/18 (78%) of HBsAg+/anti-HBe+ patients with chronic liver disease were positive for nuclear HBcAg, serum HBV DNA, or both of these markers of HBV replication. It is suggested that in long-term HBsAg carriers with serum anti-HBe and normal liver histology, viral replication is suppressed or inactive and HBV potential infectivity is presumably very low or absent. However, when viral replication is present in HBsAg+/anti-HBe+ carriers (as demonstrated by serum HBV DNA and/or nuclear HBcAg), active liver disease is often found. In these individuals, active chronic liver disease appears to be related to continued replication and secretion of HBV and may occur in a much higher proportion of HBsAg+/anti-HBe+ carriers than was previously suspected.

Adult↗

PubMed2002

Viral replication under combination antiretroviral therapy: a comparison of four different regimens.

A mathematical model of the interaction among CD4+ T-cells, HIV-1, and antiretroviral drugs was fitted to the viral load decline following initiation of combination therapy to estimate differences in the residual reproductive capacity of virus (R(0)) in the average patient in each group. Four regimens were studied: 12 patients on 5-drug nucleoside reverse transcriptase inhibitor (NRTIs), nonnucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitor (PI)-containing combination therapy, 11 patients on PI-containing triple therapy, 10 patients on double NRTI therapy, and 10 patients on NNRTI-containing triple therapy. Model fits were used to estimate R(0). The NNRTI-containing triple therapy and the 5-drug regimen blocked viral replication to the greatest extent (R(0) = 0.85; 95% confidence interval [CI], 0.79-0.91; and 0.90, 95% CI, 0.82-0.98, respectively), with the former being significantly better than the PI-containing triple regimen (R(0) = 0.98; 95% CI, 0.92-1.03; p =.007). Both the NNRTI-containing and the 5-drug regimen, as well as the PI-containing triple therapy, were significantly better at blocking viral replication than the double NRTI therapy (R(0) = 1.04; 95% CI, 1.0-1.07). Measurement of viral load after approximately 7 days provided the most accurate measure of the degree of viral suppression induced by a given drug regimen.

Adult↗

PubMed2005

Therapeutic role of CD8+ T cells in HIV-1 infection: targets and suppressors of viral replication.

CD8+ T cells are pivotal in controlling viral replication in HIV-1-infected subjects. However, in chronic infection, HIV-1-specific CD8+ T cells fail to adequately control infection, presenting incomplete maturation and more severe functional impairment with advanced disease. Accumulating evidence has shown that CD8+ T cells can also be productively infected by HIV-1. Whether HIV-1 infection of CD8+ T lymphocytes impacts on their antiviral activity remains to be determined. This review explores the potential mechanisms of HIV-1 infection of CD8+ T cells, its likely contribution to the immunopathogenesis of HIV-1 infection and potential therapeutic interventions.

Animals↗

PubMed1990

[Encephalitis with viral replication. Clinical aspects, prognosis and treatment].

Encephalites with viral replication are due to multiplication of a virus within the central nervous system. Diagnosis and initial therapeutic decisions rest on simple clinical and paraclinical findings: age of the child, presence of high-grade fever, presence and localization of seizures, CSF characteristics, and EEG findings. Acyclovir is always indicated in a drowsy child with a high fever who has even a brief seizure and CSF abnormalities.

Adolescent↗

PubMed2001

Cardioselective infection with coxsackievirus B3 requires intact type I interferon signaling: implications for mortality and early viral replication.

BACKGROUND: Interferons (IFNs) play an important role in antiviral defense and have therapeutic potential in coxsackievirus heart disease. However, little is known about the relative contributions of type I and type II IFN signaling in coxsackievirus B3 (CVB3) infection or their role in the cardioselective nature of CVB3 infection. METHODS AND RESULTS: Wild-type mice and mice deficient for either the type I or the type II IFN receptor (IFNR) were infected with CVB3. Infection of the type I IFNR-deficient mice with >10(3) plaque-forming units (pfu) of CVB3 resulted in 100% mortality within 2 to 4 days after infection. Death was rare in wild-type and type II IFNR-deficient mice after inoculation with as much as 10(8) pfu of CVB3. Surprisingly, the early mortality in the type I IFNR-deficient mice was not accompanied by higher virus titers in the heart. Unexpectedly, a dramatic increase of viral RNA in the liver was found to correlate with early mortality in type I IFNR-deficient mice. CONCLUSIONS: Type I but not type II IFN signaling is essential for the prevention of early death due to CVB3 infection. Interestingly, neither type I or type II IFN signaling has a dramatic effect on early viral replication in the heart. However, lethal viral replication in the liver is controlled by type I IFNs. These results demonstrate that the IFN system is capable of modulating both viral pathogenicity and tissue tropism.

Animals↗

PubMed2000

Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses.

Studies of potent antiretroviral combination regimens were undertaken in young infants to evaluate the potential for long-term suppression of viral replication and to evaluate the immune consequences of such therapies. Early combination antiretroviral therapy led to a loss of plasma viremia, cultivable virus, and labile extrachromosomal replication intermediates. Despite preservation of immune function, persistent human immunodeficiency type 1 (HIV-1)-specific immune responses were not detected in most infants. The absence of detectable, persisting immune responses in most HIV-1-infected infants treated early contrasts with what is typically seen in adults who are treated early. These results are consistent with the notion that early combination antiretroviral therapy of HIV-1-infected infants allows the long-term suppression of viral replication.

Anti-HIV Agents↗

PubMed1992

Effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 and hepatitis B viral replication.

This study examined the effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 infection and hepatitis B viral replication. Twenty-five chronic HBsAg carriers were studied. Presence of hepatitis B virus DNA and expression of HBeAg were more frequent among 20 chronic HBsAg carriers positive for human immunodeficiency virus type-1 antibody compared with five chronic HBsAg carriers negative for human immunodeficiency virus type-1 antibody, but the associations were not statistically significant. Hepatitis B virus DNA and HBeAg were inversely related to duration of hepatitis B virus infection (p less than 0.001). Stratifying for duration of hepatitis B virus infection, the presence of viral replication was similar among patients negative and positive for antibody to human immunodeficiency virus type-1. Hepatitis B virus DNA levels did not increase with the decline of cellular immunity over time. In conclusion, hepatitis B virus replication among chronic carriers may be a function of duration of hepatitis B virus infection rather than of an effect of human immunodeficiency virus type-1.

Acquired Immunodeficiency Syndrome↗