Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD8+ cells from HIV-infected individuals inhibit HIV replication in cultured CD4+ cells by a nonlytic, non-MHC-restricted mechanism. The activity appears to be mediated in part by a soluble antiviral factor (CAF) secreted by the CD8+ cells. In an attempt to identify this factor a large panel of recombinant cytokines was examined for their effect on HIV replication in CD4+ cells. In addition to interferon-alpha and -beta, TNF alpha, TGF beta, and IL-8 reduced virus replication in a dose-dependent fashion. In some cases, the effect of the cytokine was also dependent on the HIV infection assay used to measure it. Antibodies against the inhibitory cytokines, as well as antibodies against TNF beta, IFN-alpha, IFN-beta, IL-4, and IL-6 did not inactivate the antiviral effect of CAF. The data suggest that CAF does not have identity with known antiviral cytokines and therefore CAF may be a novel antiviral factor.
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PMID:Effect of cytokines on HIV replication in CD4+ lymphocytes: lack of identity with the CD8+ cell antiviral factor. 790 3

Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cells by murine leukemia virus (MLV)-based vectors encoding antiviral constructs such as the rev m10 dominant negative mutant or a ribozyme directed against the CAP site of HIV-1 RNA. We examined the efficiency and stability of transduction of CD4+ T cells derived from HIV-infected patients at different stages in the progression of their disease, from seroconversion to AIDS. CD4+ T cells from HIV-positive patients and uninfected donors were transduced with MLV-based vectors encoding beta-galactosidase and an intracellular antibody directed against gp120 (sFv 105) or Tat. (sFvtat1-Ckappa). The expression of marker genes and the effects of the antiviral constructs were monitored in vitro in unselected transduced CD4+ T cells. Efficiency and stability of transduction varied during the course of HIV infection; CD4+ T cells derived from asymptomatic patients were transducible at higher efficiencies and stabilities than CD4+ T cells from patients with acquired immunodeficiency syndrome (AIDS). Expression of the anti-tat intracellular antibody was more effective at stably inhibiting HIV-1 replication in transduced cells from HIV-infected individuals than was sFv 105. The results of this study have important implications for the development of a clinically relevant gene therapy for the treatment of HIV-1 infection.
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PMID:Inhibition of human immunodeficiency virus replication and growth advantage of CD4+ T cells from HIV-infected individuals that express intracellular antibodies against HIV-1 gp120 or Tat. 952 10

This article describes the Client Adherence Profiling-Intervention Tailoring (CAP-IT) intervention designed to enhance adherence to HIV/AIDS medications and reports the results of a pilot study aimed at assessing the feasibility of CAP-IT. Initially, CAP-IT was designed to be implemented by nurse case managers during regularly scheduled home visits; it is currently under revision for use in an outpatient, ambulatory care setting. CAP-IT is an innovative, structured nursing assessment and care-planning activity that allows a standardized assessment of client needs and tailored highly active antiretroviral therapy adherence intervention strategies. CAP-IT is significantly different from the current standard nursing case management practice. Pilot study results in a sample of 10 home care patients suggests that clients have knowledge and skill deficits related to adherence and in the management of the side effects of medications. In addition, the pilot study supported the acceptability of the protocol to clients and the feasibility of integrating CAP-IT into nurse case manager practice. The pilot study results also provided evidence for the efficacy of CAP-IT. The next steps include testing CAP-IT in a randomized clinical trial to determine its effectiveness.
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PMID:The Client Adherence Profiling-Intervention Tailoring (CAP-IT) intervention for enhancing adherence to HIV/AIDS medications: a pilot study. 1067 5

Granzymes are a family of serine proteinases commonly found in the granules of CD8+ T cells. In HIV infection, CD8+ cells show cytotoxic and noncytotoxic antiviral activities. The latter is mediated, at least in part, by a secreted CD8+ cell antiviral factor, CAF. Because of the antiviral nature of CD8+ cells, we examined the potential anti-HIV activity of free granzymes that can be found in CD8+ cell culture fluids. Pretreatment of CD4+ T cells with granzyme A or granzyme B had no effect on their susceptibility to infection with HIV, nor did incubation of the granzymes with HIV virions alter their infectivity. Continuous culture of acutely infected CD4+ T cells with granzyme A or B showed no effect on cell viability or the replication of HIV. The findings of this study suggest that free granzymes do not control HIV infection and spread in CD4+ T cells.
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PMID:HIV virions and HIV infection in vitro are unaffected by human granzymes A and B. 1071 74

CD8(+) lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4(+) T cells by a noncytolytic mechanism involving secreted CD8(+)-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4(+) T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector phase. Furthermore, using an Epstein-Barr virus (EBV)-specific CTL line from an HIV-seronegative donor, we demonstrated that the ability to inhibit HIV replication in a noncytolytic manner is not restricted to HIV-specific effector cells; indeed, EBV-specific CTL were as efficient as HIV-specific effectors in suppressing R5 or X4 HIV-1 strain replication in vitro. This HIV-suppressive activity mediated by a soluble factor(s) present in the culture supernatant was detectable for up to 14 days following stimulation of EBV-specific CD8(+) cells with the cognate epitope peptide. Following acute infection of CEM cells with an X4 strain of HIV-1, EBV-specific CTL line supernatant containing HIV-suppressive activity did not block virus entry but was shown to interfere with virus replication after the first template switching of reverse transcription. Our results suggest that the noncytolytic control of HIV replication by EBV-specific CD8(+) T lymphocytes corresponded to a CAF-like activity and thus demonstrate that CAF production may not be restricted to CTL induced during HIV disease. Moreover, CAF acts after reverse transcription at least for X4 isolate replication inhibition.
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PMID:CD8(+)-Cell antiviral factor activity is not restricted to human immunodeficiency virus (HIV)-specific T cells and can block HIV replication after initiation of reverse transcription. 1077 81

Jay A. Levy, MD, of the Cancer Research Institute at the University of California at San Francisco (UCSF), discusses his intriguing finding that a factor produced by CD8 cells stops the replication of HIV-1 in CD4 cells. Called CAF, Levy believes that this CD8-cell antiviral factor is critical in helping people infected with HIV to maintain a cellular immune response against the virus. According to Levy, with proper funding and the technical help from protein chemists, CAF will be found within a year. Once isolated, the researchers can begin to synthesize it and to think about possible clinical trials. Levy also discusses the progression of HIV infection and the possibility that there are two phases of infection: an initial persistent but slow replication of virus, followed by much higher viral replication and the onset of AIDS--a contradiction to the work of David Ho, George Shaw, and others.
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PMID:The CD8 cell antiviral factor: an interview with immunologist Jay Levy, MD. Interview by Mark Mascolini. 1136 40

Regulation of HIV-1 gene expression by the viral Tat transactivator is a critical step in the viral life cycle. Tat acts as a highly unusual transcription factor that interacts with a stem-loop RNA structure (TAR) found at the 5' end of all viral transcripts. There, it induces a modification of chromatin at the HIV-1 long terminal repeat (LTR) promoter and stimulates the recruitment of elongation-competent RNA polymerase II complexes capable of processive transcription. Increase of transcriptional elongation is the consequence of the interaction of Tat with cyclin T1, the cyclin component of CDK9, which phosphorylates the carboxy-terminal domain of RNA polymerase II to enhance its processivity. Tat-induced transcriptional activation of the LTR promoter is concomitant with recruitment of the transcriptional coactivators p300 and the highly homologue cAMP-responsive transcription factor binding protein (CBP). These large proteins act at the level of transcriptional initiation by bridging the basal transcription machinery with specific transcriptional activators. Furthermore, p300/CBP are histone acetyl-transferases capable of modulating the interaction of nucleosomes with DNA and with chromatin remodeling complexes. Besides histones, Tat itself is a substrate for the enzymatic activity of p300/CBP and of the associated factor P/CAF, suggesting a regulatory role of acetylation on the protein itself. Devising a unifying model for LTR activation that includes activities of Tat at the levels of both transcriptional initiation and transcriptional elongation is a challenging task at this moment. Nevertheless, protein localization studies indicate that both cyclin T1 and p300/CBP co-localize in specific subnuclear compartments, thus suggesting participation of both proteins in the formation of multimolecular complexes governing coordinated steps of transcriptional activation.
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PMID:Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator. 1154 19

CD8(+) T lymphocytes can suppress human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8(+) T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. However, the mechanism by which CAF inhibits LTR activation is not understood. Here, we show that conditioned media from several herpesvirus saimari-transformed CD8(+) T lymphocytes inhibit, in a time- and dose-dependent manner, the replication of HIV-1 pseudotype viruses that express the envelope glycoproteins of vesicular stomatitis virus (HIV-1(VSV)). The same conditioned media also inhibit phorbol myristate acetate-induced activation of the HIV-1 LTR and activate the signal transducer and activator of transcription 1 (STAT1) protein. We have obtained direct evidence that STAT1 is necessary for CAF-mediated inhibition of LTR activation and HIV-1 replication. Thus, the inhibitory effect of CAF on HIV-1(VSV) replication was abolished in STAT1-deficient cells. Moreover, CAF inhibition of LTR activation was diminished both in STAT1-deficient cells and in cells expressing a STAT1 dominant negative mutant but was restored when STAT1 was reintroduced into the STAT1-deficient cells. We also observed that CAF induced the expression of interferon regulatory factor 1 (IRF-1), and that IRF-1 gene induction was STAT-1 dependent. Taken together, our results suggest that CAF activates STAT1, leading to IRF-1 induction and inhibition of gene expression regulated by the HIV-1 LTR. This study therefore helps clarify one molecular mechanism of host defense against HIV-1.
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PMID:A soluble factor(s) secreted from CD8(+) T lymphocytes inhibits human immunodeficiency virus type 1 replication through STAT1 activation. 1175 48

The aim of this protocol is to establish a common basis for the production of reference values and well-defined and documented reference intervals for plasma proteins, based on common standardization, using the IFCC/BCR/CAP Certified Reference Material CRM 470. The strategy is to search for racial and environmental/geographical similarities and sources of differences in order to describe the main causes for variability among smaller or larger groups in selected societies and to estimate the sizes of differences for the different proteins according to the investigated sources. For this purpose, groups of reference individuals are selected according to race and geographical/environmental location, e.g. African Americans and Caucasians from the US. The reference individuals are groups of approximately 160 healthy male blood donors, 20 to 60 years of age. Rule-out criteria are positivity for HIV, hepatitis B and C antibodies and blood hemoglobin below the lower reference limit. Exclusion in relation to different C-reactive protein (CRP) levels will be investigated. Coagulation, storage conditions, transport, and the procedure for thawing are specified. The laboratories undertaking the measurements must have adequate analytical performance, and calibration and quality of performance are defined and documented, together with recommended control materials and procedures. Statistical models for describing distributions and for comparing groups are described. It is recommended that the data be presented as reference limits with 90% confidence intervals of those limits.
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PMID:Strategy for determining racial and environmental similarities and differences for plasma proteins. 1183 31

The increased incidence of HIV/AIDS disease in women aged 15 - 49 years has identified the urgent need for a female-controlled, efficacious and safe vaginal topical microbicide. To meet this challenge, new topical microbicide candidates consisting of molecules or formulations that modify the genital environment (BufferGel, engineered Lactobacillus, over-the-counter lubricants), surfactants (C31D/Savvy, sodium dodecyl sulfate, sodium lauryl sulfate), polyanionic polymers (PRO 2000, beta-cyclodextrin, Carraguard, CAP, D2S, SPL-7013), proteins (cyanovirin-N, monoclonal antibodies, thromspondin-1 peptides, Pokeweed antiviral protein and others), reverse transcription inhibitors (PMPA [Tenofovir ]), UC-781, SJ-3366, DABO and thiourea) and other molecules (NCp7-specific virucides, chemokine receptor agonists/antagonists, WHI-05 and WHI-07) are currently being investigated for activity, safety and efficacy. This review will assess the development of these molecules in the context of cervicovaginal defences and the clinical failure of nonoxynol-9.
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PMID:Considerations and development of topical microbicides to inhibit the sexual transmission of HIV. 1215 Jul 3


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