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At least 775 records · Page 43Linked to original sources
PubMed1986

T lymphocyte subsets implicated in cytotoxicity in autologous hepatocytes in chronic active hepatitis patients with active viral replication.

We investigated inhibitory effect of various monoclonal antibodies on T-cell-mediated cytotoxicity against autologous hepatocytes in 24 patients with hepatitis B surface antigen/hepatitis B e antigen (HBsAg/HBeAg)-positive chronic active hepatitis. A significant reduction of cytotoxicity index occurred after preincubation of T lymphocytes with anti-Leu 7 (killer-natural killer cells), D1/12 (Ia-positive cells), 5/9 (restricted helper/inducer cells), and MLR4 ("activated" and radiosensitive helper cells) monoclonal antibodies (MAb). Anti-Leu 2a (cytotoxic/suppressor cells) and anti-Leu 3a (helper/inducer cells) MAb did not affect cytotoxic activity. This finding supports the hypothesis that the T cytotoxic reaction in this in vitro system is probably due to two mechanisms: first, spontaneous cell membrane cytotoxicity sustained by anti-Leu-7-positive lymphocytes; and second, specific cytotoxicity mediated by activated Ia-positive cells. We also found that the presence of helper/inducer cells (5/9 positive) appears to be a prerequisite for the cytotoxic reaction.

Adult↗
PubMed1988

Effect of rolling on foci development and viral replication for herpes simplex virus (HSV).

The effect of rolling on the number of herpes simplex virus (HSV) foci and yield of infectious virus was examined for cultures inoculated with clinical specimens. Inoculated cultures were either rolled at 2 revolutions per minute (rpm) or held stationary. Cultures that were rolled at 2 rpm showed a significantly greater number of foci and plaque forming units (PFU) over stationary cultures. The geometric mean fold increase in PFU between rolled and stationary cultures was 8-fold. Rolling of inoculated cultures should be used in the clinical virology laboratory to aid in the rapid detection of HSV.

Cell Line↗
PubMed1994

Cytokine regulation of lactate dehydrogenase-elevating virus: inhibition of viral replication by interferon-gamma.

The mechanisms which regulate the replication of lactate dehydrogenase-elevating virus (LDV), a persistent murine model virus which infects macrophages, are unclear. For this study, the effects of murine recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on LDV replication were examined. LDV permissiveness was reduced in macrophages obtained from uninfected mice treated with IFN-gamma prior to cell harvest and in vitro LDV infection. Virus inhibition by IFN-gamma was also observed when neonatal LDV-infected mice were injected with this cytokine prior to macrophage harvest and analysis of LDV replication-positive cells. Persistently LDV-infected mice demonstrated an increase in viremia levels following treatment with TNF-alpha. Neither IFN-gamma nor TNF-alpha had any direct in vitro effect on LDV replication in cultured macrophages, suggesting that the actions of these cytokines required secondary or accessory in vivo events. These results provide evidence for cytokine-mediated regulation of LDV infection and support a role for the immune system in the LDV-host relationship.

Animals↗
PubMed1992

Macrophages, mycobacteria and HIV: the role of cytokines in determining mycobacterial virulence and regulating viral replication.

The marriage of two scourges, one old (mycobacterial disease) and one new (HIV), has presented an enormous challenge to the medical and public health communities, and has stirred renewed interest in mechanisms for immune control of mycobacterial infection. Virulence of both M. avium and M. tuberculosis appears to be inversely related to the capacity of the microorganisms to induce production of protective cytokines in infected hosts. TNF alpha and IFN gamma are central to this process, and mycobacterial polysaccharides may be their main determinant. Despite these similarities, M. tuberculosis and M. avium cause illnesses at the polar extremes of HIV disease. Tuberculosis, occurring early in the course of HIV disease, may promote HIV replication in otherwise latently infected cells via induction of cytokines. As such, the potential exists for accelerated progression to AIDS due to the mutual synergy of these pathogens.

AIDS-Related Opportunistic Infections↗
PubMed2004

Tryptophan scanning mutagenesis of aromatic residues within the polymerase domain of HIV-1 reverse transcriptase: critical role of Phe-130 for p51 function and second-site revertant restoring viral replication capacity.

The effects on virus viability and reverse transcriptase (RT) function of substituting Trp for Tyr or Phe residues within the polymerase domain of human immunodeficiency virus type 1 (HIV-1) RT have been analyzed with an infectious HIV-1 clone. Viruses containing mutations Y56W, F61W, F87W, F116W, Y127W, Y144W, F171W, Y181W, Y183W, Y188W, F227W, or Y232W in their RT-coding regions were viable and showed replication capacities similar or slightly reduced in comparison with the wild-type HIV-1. However, RTs bearing mutations F77W or Y146W had a dNTP-binding defect, rendering nonviable viruses. HIV-1 carrying RT mutations F124W or F130W replicated very poorly, but compensatory changes (K83R for F124W, and T58S for F130W) were selected upon passaging the virus in cell culture. The amino acid substitution F130W diminishes the stability of the 51-kDa subunit of the RT (p51) and impairs polyprotein processing in virus-infected cells, an effect that can be mitigated when T58S is found in p51.

Animals↗
PubMed2004

Analysis of a viral replication repressor: sequence requirements for a large symmetrical internal loop.

Nearly all members of the Carmovirus genus contain a structurally conserved 3' proximal hairpin (H5) with a large internal symmetrical loop (LSL). H5 has been identified as a repressor of minus-strand synthesis in a satellite RNA (satC), which shares partial sequence similarity with its helper virus Turnip crinkle virus (TCV). Repression was due to sequestration of the 3' end mediated by base pairing between 3' end sequence and the 3' side of the LSL (G. Zhang, J. Zhang and A. E. Simon, J. Virol., in press). Single site mutational analysis and in vivo genetic selection (SELEX) of the 14 base satC H5 LSL indicated specific sequences in the middle and upper regions on both sides of the LSL are necessary for robust satC accumulation in plants and protoplasts. Fitness of wild-type satC and satC LSL mutants to accumulate in plants, however, did not necessarily correlate with the ability of these RNAs to replicate in protoplasts. This suggests that the LSL might be involved in processes in addition to repression of minus-strand synthesis.

3' Untranslated Regions↗
PubMed2004

Conserved residues in the coiled-coil pocket of human immunodeficiency virus type 1 gp41 are essential for viral replication and interhelical interaction.

The human immunodeficiency virus type 1 (HIV-1) gp41 plays an important role in mediating the fusion of HIV with host cells. During the fusion process, three N-terminal helices and three C-terminal helices pack in an anti-parallel direction to form a six-helix bundle. X-ray crystallographic analysis of the gp41 core demonstrated that within each coiled-coil interface, there is a deep and large pocket, formed by a cluster of residues in the N-helix coiled-coil. In this report, we systematically analyzed the role of seven conserved residues that are either lining or packing this pocket on the infectivity and interhelical interaction using novel approaches. Our results show that residues L568, V570, W571, and K574 of the N-helix that are lining the side chain and right wall of the pocket are important for establishing a productive infection. Mutations V570A and W571A completely abolished replication, while replication of the L568A and K574A mutants was significantly attenuated relative to wild type. Similarly, residues W628, W631, and I635 of the C-helix that insert into the pocket are essential for infectivity. The impaired infectivity of these seven mutants is in part attributed to the loss in binding affinity of the interhelical interaction. Molecular modeling of the crystal structure of the coiled-coil further shows that alanine substitution of those residues disrupts the hydrophobic interaction between the N- and C-helix. These results suggest that the conserved residues in the coiled-coil domain play a key role in HIV infection and this coiled-coil pocket is a good target for development of inhibitors against HIV. In addition, our data indicate that the novel fluorescence polarization assay described in this study could be valuable in screening for inhibitors that block the interhelical interaction and HIV entry.

Amino Acid Sequence↗
PubMed2006

Recombinant adenoviral vectors turn on the type I interferon system without inhibition of transgene expression and viral replication.

Recombinant adenovirus administration gives rise to transgene-independent effects caused by the ability of the vector to activate innate immunity mechanisms. We show that recombinant adenoviruses encoding reporter genes trigger IFN-alpha and IFN-beta transcription from both plasmacytoid and myeloid mouse dendritic cells. Interestingly, IFN-beta and IFN-alpha5 are the predominant transcribed type I IFN genes both in vitro and in vivo. In human peripheral blood leukocytes type I IFNs are induced by adenoviral vectors, with a preponderance of IFN-beta together with IFN-alpha1 and IFN-alpha5 subtypes. Accordingly, functional type I IFN is readily detected in serum samples from human cancer patients who have been treated intratumorally with a recombinant adenovirus encoding thymidine kinase. Despite inducing functional IFN-alpha release in both mice and humans, gene transfer by recombinant adenoviruses is not interfered with by type I IFNs either in vitro or in vivo. Moreover, IFN-alpha does not impair replication of wild-type adenovirus. As a consequence, cancer gene therapy strategies with defective or replicative-competent adenoviruses are not expected to be hampered by the effect of the type I IFNs induced by the vector itself. However, type I IFN might modulate antitumor and antiadenoviral immune responses and thus influence the outcome of gene immunotherapy.

Adenoviridae↗
PubMed2002

The role of hepatitis B virus-specific memory CD8 T cells in the control of viral replication.

BACKGROUND/AIMS: The aim of this study is to clarify the differences of host immune responses between acute self-limited and chronic persistent hepatitis B virus (HBV) infections by quantitative and qualitative analysis of HLA-A*2402-restricted HBV-specific CD8+ T cells. METHODS: HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HBV were analyzed by flow cytometry using two HLA-A*2402-HBV peptide tetrameric complexes. RESULTS: High numbers of HBV-specific CD8+ T cells were detected in acute phase PBMCs from most individuals with acute HBV infection while the number of these cells was greatly reduced in recovery phase PBMCs. HBV-specific CD8+ T cells were not detected in PBMCs from individuals with chronic HBV infection except for one patient during acute exacerbation. HBV-specific CD8+ T cells were induced by in vitro peptide stimulation in PBMCs from chronic HBV carriers with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. CD28CD45RA phenotype analysis showed that HBV-specific CD8+ T cells in acute phase PBMCs predominantly express a memory T cell phenotype. CONCLUSIONS: HBV-specific memory CD8+ T cells may play a crucial role in complete clearance of HBV from patients with acute HBV hepatitis.

Acute Disease↗
PubMed1986

The use of corticosteroids in conjunction with antiviral therapy in chronic hepatitis B with ongoing viral replication.

Eleven patients with hepatitis B e antigen (HBeAg)-positive chronic active hepatitis B were treated with an 8-wk course of prednisone followed by 28 days of adenine arabinoside 5'-monophosphate. Five individuals had a complete response (loss of HBeAg and DNA polymerase) whereas 3 had a partial response (sustained loss of DNA polymerase but persistence of HBeAg). At the present time 27 +/- 3 mo has elapsed since the completion of therapy, and 4 of 5 complete responders remain negative for replicative markers while the fifth person exhibited transient reactivation of infection. Elevated DNA polymerase has reappeared in two of the three partial responders, in one 22 mo after completion of therapy. These encouraging results have led to a randomized, controlled trial using short-term prednisone followed by recombinant alpha-interferon.

Adult↗
PubMed1997

Induction of interleukin-1 and glucocorticoid hormones by HIV promotes viral replication and links human chromosome 2 to AIDS pathogenesis: genetic mechanisms and therapeutic implications.

Human immunodeficiency virus may regulate its replication by stimulating the synthesis of interleukin-1. Interleukin-1, in turn, has the ability to stimulate the human immunodeficiency virus enhancer region. The human genes responsible for interleukin-1 and interleukin-1 receptor antagonist synthesis are located on the long arm of chromosome 2. Coincidentally, the trans-activation responsive ribonucleic acid element in the R region of the long terminal repeat of human immunodeficiency virus-1 has been found to interact directly with a factor present on the long arm of chromosome 2 to facilitate transactivation by the human immunodeficiency virus Tat protein. The human CD26 gene is also located on the long arm of chromosome 2. CD26 is a lymphocyte cell surface antigen that is stimulated by interleukin-1 and serves with CD4 as a coreceptor that interacts with the V3 loop in gp120 of human immunodeficiency virus. The human immunodeficiency virus-induced interleukin-1 excess, thus, serves human immunodeficiency virus by enhancing replication, and by increasing human immunodeficiency virus infectivity via activation of CD26. IL-1 also adversely affects acquired immune deficiency syndrome-related Kaposi's sarcoma. Several genetic treatments for human immunodeficiency virus infection are proposed.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Adenine and deazaadenine nucleoside and deoxynucleoside analogues: inhibition of viral replication of sheep MVV (in vitro model for HIV) and bovine BHV-1.

A series of N(6)-cycloalkyl-2',3'-dideoxyadenosine derivatives has been prepared by coupling of 2,6-dichloropurine to protected 2,3-dideoxyribose, followed by reaction with appropriate cycloalkylamines. Synthesized compounds, along with other purine nucleoside analogues previously synthesized in our laboratory, have been tested for their antiviral activity against Bovine herpesvirus 1 (BHV-1) and sheep Maedi/Visna Virus (MVV), the latter being an in vitro and in vivo model of Human Immunodeficiency Virus (HIV). All compounds showed good antireplicative activity against MVV, with the N(6)-cycloheptyl-2',3'-dideoxyadenosine (5b) being the most active [effective concentration (EC(50)) causing 50% reduction of cytopatic effects (CPE)=27 nM]. All compounds showed also a from low to very low cell toxicity, resulting in a cytotoxic dose 50 (CD(50))/EC(50) ratio in some cases higher than 1000.

Animals↗