HIV-1 envelope glycoproteins-mediated apoptosis is regulated by CD4 dependent and independent mechanisms.

The progressive loss of CD4 T lymphocytes is one of the hallmarks of HIV infection. The reverse correlation observed in vivo, between plasmatic HIV levels and CD4 T lymphocyte counts, supports the concept that direct HIV-mediated cell death contributes to this depletion. Previously, we and others have demonstrated, in vitro, that interactions between membrane-expressed HIV-envelope glycoprotein complexes and CD4 ecto-molecules are critical to cell killing which occurs mainly by apoptosis.

HIV-2 EHO isolate has a divergent envelope gene and induces single cell killing by apoptosis.

The human immunodeficiency virus type 2 (HIV-2)-related isolate, referred to as HIV-2 EHO, has been isolated from an Ivory Coast patient with acquired immunodeficiency syndrome (AIDS). Infection of CD4 expressing cells with this highly infectious virus mediates a cytopathic effect characterized by single-cell killing as a consequence of apoptosis. Nucleotide sequence analysis of the HIV-2 EHO genome revealed a significant degree of divergence of its envelope gene from that of other known HIV-2 strains.

The cytopathic effect of human immunodeficiency virus is independent of high levels of unintegrated viral DNA accumulated in response to superinfection of cells.

Large quantities of genome-sized viral DNA are detected in the nucleoplasm of CD4+ T cells infected with human immunodeficiency virus type 1 (HIV-1). This unintegrated HIV DNA is in the form of both circular and linear species. Accumulation of such DNA occurs gradually during a 5 day HIV infection and is correlated with the proportion of cells involved in the production of HIV proteins.

Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells.

The cytopathic effect of HIV-1 and HIV-2 in CD4+ lymphocytes has been shown to be associated with apoptosis or programmed cell death. Using different experimental conditions, we demonstrate here that apoptosis is triggered by cell membrane expression of the mature HIV envelope glycoproteins, gp120-gp41 complex, and their interaction with CD4 receptor molecules. Viral entry alone did not induce apoptosis but virus replication was required in order to produce the gp120-gp41 complex.

Direct and indirect mechanisms mediating apoptosis during HIV infection: contribution to in vivo CD4 T cell depletion.

The gradual depletion of CD4+ T lymphocytes during the development of AIDS may be due, at least in part, to a process referred to as apoptosis. This process involves a Ca2+ dependent nuclear endonuclease that cleaves the chromatin at internucleosomal junctions. In addition, we have recently provided evidence that apoptosis may be responsible not only for the progressive loss of CD4+ T lymphocytes but may be operative in CD8+ T lymphocytes as well.

Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients.

Objective: To analyse serological aspects of systemic autoimmunity in HIV-1-seropositive patients and in individuals at risk for AIDS.

Design And Methods: The reactivity of antibodies in the serum of 100 HIV-1-seropositive patients was investigated by enzyme-linked immunosorbent assay (ELISA) using a series of antigens known to be recognized by antibodies from patients with multisystemic autoimmune diseases, such as systemic lupus erythematosus, mixed-connective tissue disease and Sjögren's syndrome.

Results: High levels of immunoglobulin G (IgG) antibodies reacting with double-stranded DNA (dsDNA), synthetic peptides of ubiquitinated histone H2A, Sm-D antigen, U1-A RNP antigen and 60 kD SSA/Ro antigen were found in 44-95% of HIV-infected patients.

Antiviral action of polyadenylic-polyuridylic acid against HIV in cell cultures.

Polyadenylic-polyuridylic acid referred to as poly(A).poly(U) is a synthetic double-stranded RNA which has been shown to manifest both antitumoral and immunomodulatory activities. Here we used this agent to demonstrate its antiviral activity against the human immunodeficiency virus (HIV-1 and HIV-2).

The cytopathic effect of HIV is associated with apoptosis.

Large amounts of histones, H1, H2A, H2B, H3, and H4, were observed in total extracts of T4 lymphocytes and derived cell lines infected with the human immunodeficiency virus (HIV) type 1 or type 2. These histones were simply detectable by analysis of crude cellular extracts by polyacrylamide gel electrophoresis in SDS and staining the proteins with Coomassie blue or by immunoblot assays using specific polyclonal antibodies. The histones were found to be localized in the nucleoplasm, bound to low molecular weight (LMW) DNA in the form of nucleosomes.