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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble proteins of the human immunodeficiency virus (HIV) might play a significant role in the pathogenesis of HIV infection. The addition of synthetic Tat peptides, but not that of the recombinant Nef or Vif protein, inhibited proliferative responses of CD4+ tetanus antigen-specific, exogenous interleukin-2 (IL-2)-independent T-cell clones in a dose-dependent manner. In addition, Tat peptides inhibited the anti-CD3 monoclonal antibody-induced proliferative responses of both purified CD4+ and CD8+ T cells. Tat did not affect proliferative responses induced by phorbol myristate acetate plus ionomycin. The Tat peptides at the concentrations used (0.1 to 3 micrograms/ml) did not affect the viability of the cells as determined by trypan blue exclusion. Treatment of Tat peptides with polyclonal Tat antibodies abrogated the inhibitory effect of Tat. Soluble Tat proteins secreted by HeLa cells transfected with the tat gene also inhibited antigen-induced proliferation of the T-cell clones. Tat inhibited the anti-CD3 monoclonal antibody-induced IL-2 mRNA expression and IL-2 secretion but did not affect IL-2 receptor alpha-chain mRNA or protein expression on peripheral blood T cells. Finally, treatment of T-cell clones with the Tat peptide did not affect the antigen-induced increase in intracellular calcium, hydrolysis of phosphatidyl inositol to inositol trisphosphate, or translocation of protein kinase C from the cytosol to the membrane. These studies demonstrate that the mechanism of the Tat-mediated inhibition of T-cell functions involves a phospholipase C gamma 1-independent pathway.
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PMID:Human immunodeficiency virus Tat induces functional unresponsiveness in T cells. 798 46

The [Tyr5,12,Lys7]-polyphemusin II peptide (T22) has been shown to inhibit HIV-1 replication in lymphocytes. The mechanism of T22 inhibition of HIV-1 replication is not known but may involve T22 competition with HIV-1 for attachment sites on the plasma membrane of targeted cells. Here we find that three human immunocyte cell lines (H9, Jurkat, and U-937) attach to T22. The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), has been shown to activate intracellular protein kinase C and to stimulate lymphocyte attachment to various substrates through specific cell surface receptors. Here we find that TPA treatment enhances attachment of the immunocytes to T22 by three- to four-fold. These data demonstrate that T22 binds to immunocyte cell surfaces and support the hypothesis that T22 may inhibit HIV-1 replication by competing with the virus for a common cell surface receptor(s).
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PMID:Lymphocytes and promonocytes attach to the synthetic [Tyr5,12, Lys7]- polyphemusin II peptide. 803 49

The nef genes of the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) and the related simian immunodeficiency viruses (SIVs) encode a protein (Nef) whose role in virus replication and cytopathicity remains uncertain. As an attempt to elucidate the function of nef, we characterized the nucleotide and corresponding protein sequences of naturally occurring nef genes obtained from several HIV-1-infected individuals. A consensus Nef sequence was derived and used to identify several features that were highly conserved among the Nef sequences. These features included a nearly invariant myristylation signal, regions of sequence polymorphism and variable duplication, a region with an acidic charge, a (Pxx)4 repeat sequence, and a potential protein kinase C phosphorylation site. Clustering of premature stop codons at position 124 was noted in 6 of the 54 Nef sequences. Further analysis revealed four stretches of residues that were highly conserved not only among the patient-derived HIV-1 Nef sequences, but also among the Nef sequences of HIV-2 and the SIVs, suggesting that Nef proteins expressed by these retroviruses are functionally equivalent. The "Nef-defining" sequences were used to evaluate the sequence alignments of known proteins reported to share sequence similarity with Nef sequences and to conduct additional computer-based searches for similar protein sequences. A gene encoding the consensus Nef sequence was also generated. This gene encodes a full-length Nef protein that should be a valuable tool in further studies of Nef function.
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PMID:Analysis of human immunodeficiency virus type 1 nef gene sequences present in vivo. 804 40

Starting from our previous observations that the HIV-1-mediated engagement of CD4 induced apoptotic death of TF-1 hematopoietic progenitor cells, in this study we evaluated PKC activity and intracellular Ca2+ levels in TF-1 cells treated with viable and heat-inactivated HIV-1 (strain IIIB) or anti-CD4 Leu3a monoclonal antibody (mAb). Both viable and heat-inactivated HIV-1 or anti-CD4 mAb, but not anti-human cytomegalovirus (HCMV) 66kD protein or anti-CD8 mAb induced a rapid (5-10 min) increase in PKC activity under both serum-containing and serum-free conditions. The same treatment also induced both a transient and a long-lasting (48 hours) decrease (p < 0.05) in intracellular Ca2+ levels in serum-containing cultures. We propose that the observed changes in PKC activity and intracellular Ca2+ levels might be involved in the HIV-1 mediated apoptosis of hematopoietic progenitor cells.
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PMID:CD4 engagement by HIV-1 in TF-1 hematopoietic progenitor cells increases protein kinase C activity and reduces intracellular Ca2+ levels. 806 78

HIV-1 Tat has been shown to have an inhibitory effect on the Ag-specific responsiveness of human peripheral T cells. We have previously demonstrated that this retroviral protein binds to and partially inhibits the enzymatic activity of dipeptidyl aminopeptidase type IV (DP IV), also known as CD26, which is expressed on a variety of mammalian tissue, including T lymphocytes. A number of studies have implicated a role for DP IV in the activation of T lymphocytes. By utilizing HIV-1 Tat, as well as ProboroPro, a potent and specific boronic acid analog inhibitor of DP IV, we show here that blocking DP IV partially inactivates Ag and anti-CD3-mediated T cell proliferation. Neither mitogen nor anti-CD2 mediated proliferation of T lymphocytes, however, is impaired by blocking DP IV. The target molecule for the inhibition induced by both compounds was confirmed by the finding that soluble DP IV neutralized the reduced Ag responsiveness. The Ag-specific inhibition could be overcome by the addition of exogenous IL-2, suggesting that blocking or inactivation of DP IV results in a state of anergy, probably by interfering with the delivery or amplification of a signal necessary for IL-2 production. This is further substantiated by the finding that costimulation of human PBMC via the CD28 molecule, which initiates a non-TCR-dependent signaling pathway, overcomes the reduced Ag responsiveness induced by Tat and ProboroPro. The fact that ProboroPro has no impact on stimulation of T cells with PMA and ionomycin implies that blocking DP IV is influencing events before the activation of protein kinase C and Ca2+ flux. These results suggest that DP IV is necessary for amplification of signals generated by the engagement of the TCR-CD3 complex by nominal Ag.
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PMID:Mechanism of HIV-1 Tat induced inhibition of antigen-specific T cell responsiveness. 809 14

With T-cell lines constitutively expressing Nef from the SF2 strain of human immunodeficiency virus type 1 (HIV-1SF2) in the form of a hybrid CD8-Nef fusion protein or T-cell lines chronically infected with HIV-1SF2, a cellular serine kinase was found that specifically associates with Nef. Proteins of 62 kDa and 72 kDa, which coimmunoprecipitated with Nef, were phosphorylated in in vitro kinase assays. This Nef-associated serine kinase activity was not blocked by inhibitors of protein kinase C or protein kinase A and was lost when Nef was truncated at amino acid 94 or 99. These findings present evidence that a serine kinase activity is associated with Nef expressed in human T lymphocytes.
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PMID:Human immunodeficiency virus type 1 Nef associates with a cellular serine kinase in T lymphocytes. 810 42

To delineate cellular genes that are required for optimal HIV-1 infection, CEM cells were subjected to treatment with the chemical mutagen ethylmethanesulfonate (EMS) and subclones were selected based on their increased resistance to HIV-1 infection and reduced syncytium formation, despite relatively normal CD4 expression (20,000 to 25,000 receptors/cell). Two subclones with this phenotype demonstrated a diminished capacity of HIV-1 long terminal repeat-chloramphenicol acetyl transferase expression either after treatment with the protein kinase C activator PMA, or through Tat-mediated transactivation. In this study, we show that the cellular levels of the NF-kappa B DNA binding proteins (but not AP1 or SP1) are markedly reduced in these cell mutants both at the mRNA and protein levels, resulting in reduced nuclear localization of p50/p65 after PMA induction or treatment with the lymphokine TNF-alpha. Transient reconstitution with a plasmid expressing p50 resulted in partial recovery of PMA-inducible LTR-chloramphenicol acetyl transferase expression. These data suggest that, at least in the CEM T cell line, a selective reduction in the NF-kappa B DNA binding proteins is sufficient to curtail HIV-1 infection.
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PMID:Chemically selected subclones of the CEM cell line demonstrate resistance to HIV-1 infection resulting from a selective loss of NF-kappa B DNA binding proteins. 814 79

T-cell-dependent B cell differentiation involves two phases: an inductive phase of T cell activation followed by an effector phase, which involves stimulation of B cells by activated T cells. We have previously demonstrated that anti-CD3 mAb and antigen-induced T-cell-dependent B cell functions are inhibited by HIV-1 envelope glycoprotein, gp120, at the inductive phase of T-cell-dependent B cell response. In this study we have investigated whether gp120 also inhibits the effector phase of interactions involved in T-cell-dependent-B cell differentiation response. For these studies, CD4+ T cells were first activated with antigen or pokeweed mitogen, cultured with soluble HIV-gp120 or medium for 2 hr, and washed. Coculture of gp120-treated preactivated T cells with autologous B cells resulted in impairment of IgG secretion, but did not affect IgM secretion significantly. The IgG secretion was restored by the addition of PMA (activator of protein kinase C) or forskolin (activator of adenylate cyclase), but not by the addition of ionomycin (inducer of intracellular calcium) to the T plus B cell cultures. A similar pattern of Ig secretion (IgM, no IgG) was observed with B cells of a patient with bare lymphocyte syndrome, indicating a requirement for MHC class II molecule interaction with T cells. These studies suggest that the effector phase of T-B cell interactions are impaired by gp120, and that the mechanism involves a signal transducing event(s), which is dependent upon cyclic AMP and/or protein kinase C. Furthermore, these latter reactions occur subsequent to T-B cell contact-dependent interactions at the effector phase, which involve MHC class II molecules on B cells and CD4 molecules on T cells.
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PMID:Envelope glycoproteins of HIV-1 interfere with T-cell-dependent B cell differentiation: role of CD4-MHC class II interaction in the effector phase of T cell help. 816 44

Betulinic acid [1] and platanic acid [2], isolated from the leaves of Syzigium claviforum, were found to be inhibitors of HIV replication in H9 lymphocyte cells. Evaluation of anti-HIV activity with eight derivatives of 1 revealed that dihydrobetulinic acid [3] was also a potent inhibitor of HIV replication. The C-3 hydroxy group and C-17 carboxylic acid group, as well as the C-19 substituents, contribute to enhanced anti-HIV activity. The inhibitory activity of these compounds against protein kinase C (PKC) was also examined, since a correlation between anti-HIV and anti-PKC activities has been suggested. However, there was no apparent correlation between anti-HIV activity and the inhibition of PKC among these compounds.
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PMID:Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids. 817 1

Synthetic peptides derived from the putative immunosuppressive region of HIV-1 gp41 were examined to identify the amino acids required for suppressive activity. The active sequence was similar to the pseudosubstrate regulatory peptide of protein kinase C and to a sequence from the cyclic immune peptides known as defensins. The activity of the gp41 peptides appeared to be dependent upon a structural conformation, possibly a looped motif like that found in defensins. This similarity to defensins, which can insert themselves into lipid bilayers, was further strengthened by demonstrating that gp41 peptides have the ability to associate with liposomes and lymphocyte membranes. These results suggest that the immunosuppressive region of gp41 may participate in the membrane interactions required for viral fusion and infectivity.
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PMID:Structural and functional similarities between synthetic HIV gp41 peptides and defensins. 820 Jan 33


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