Host membrane proteins in the HIV-induced membrane fusion: Role in pathogenesis and therapeutic potential of autoantibodies.

Host proteins such as receptors, adhesion and signaling molecules, promote virus-cell fusion, virus cell-cell transmission, and formation of multinucleated cells with outstanding properties. These events are implicated in virus dissemination and the induction of pathological effects such as the infection of the gut-associated lymphoid tissue, placenta infection, and neurological complications. Antibodies directed to the host membrane proteins are produced during the natural HIV infection and may contribute significantly to virus inhibition. Antibodies against the HIV receptor have been approved for therapy and others targeting additional host membrane proteins are currently under evaluation. This review emphasizes the relevance of the different pathways of HIV spreading between cells and of antibodies directed to host membrane components in the development of broad-range therapeutics against HIV.

Inhibition of HIV-1 envelope-dependent membrane fusion by serum antilymphocyte autoantibodies is associated with low plasma viral load.

The HIV-1 envelope protein (Env) mediates the membrane fusion process allowing virus entry to target cells and the efficiency to induce membrane fusion is an important determinant of HIV-1 pathogenicity. In addition to virus receptors, other adhesion/signaling molecules on infected and target cells and virus particles can enhance fusion. The presence of antilymphocyte autoantibodies (ALA) in HIV patients' serum suggests that they may contribute to the inhibition of Env-mediated membrane fusion. Here, sera from 38 HIV-1 infected treatment-naïve men and 30 healthy donors were analyzed for the presence of IgG and IgM able to bind to CD4-negative Jurkat cells. The use of CD4-negative cells precluded the binding of virus-antibody immune complexes, and allowed detection of ALA different from anti-CD4 antibodies. IgG and IgM antibodies binding to Jurkat CD4-negative cells was detected in 74% and 84% of HIV-positive sera, respectively. Then, the activity of sera on fusion of CD4+ with HIV Env+ Jurkat cells was determined before and after their adsorption on CD4-negative Jurkat cells to remove ALA. Sera inhibited fusion at variable extents, and inhibitory activity decreased in 58% of serum samples after adsorption, indicating that ALA contributed to fusion inhibition in these sera (herein called fusion inhibitory ALA). The contribution of ALA to fusion inhibition in individual sera was highly variable, with an average of 33%. IgG purified from a pool of HIV+ sera inhibited fusion of primary CD4 T lymphocytes with Jurkat Env+, and adsorption of IgG on CD4-negative Jurkat cells diminished the fusion inhibitory activity. Thus, the inhibitory activity of sera was related to IgG ALA. Our observations suggest that fusion inhibitory ALA other than anti-CD4 antibodies may contribute significantly to the inhibition of Env-mediated cell-cell fusion. Fusion inhibitory ALA, but not total ALA levels, associated with low plasma viral loads, suggesting that specific ALA may participate in virus containment by inhibiting virus-cell fusion in a significant fraction of HIV-infected patients.