The env Protein of an Infectious Noncytopathic HIV-2 Is Deficient in Syncytium Formation

A recent isolate of human immunodeficiency virus type 2 (HIV-2) designated HIV-2_ST is deficient in its ability to cause the typical cytopathic effects of HIV infection. The pathogenic potential of HIV-2 in inducing human disease may be less than that of HIV-1, and it is of particular interest to establish the basis for the reduced cytopathogenicity of this isolate in vitro. Utilizing recombinant vaccinia viruses (rVV) carrying the envelope genes (env) of HIV-2_ST or those of fully cytopathic HIV-1 or HIV-2 isolates, we have investigated envelope glycoprotein expression, processing, transport, and biological function. Radioimmunoprecipitation and polyacrylamide gel electrophoresis (RIP-PAGE) of rVV-infected cell lysates indicated that the proteins expressed by each recombinant were synthesized, processed, and recognized by specific antisera. Immunofluorescence studies showed that the recombinant env gene products of HIV-2_ST and HIV-2_ROD reach the cell surface and are retained there in similar amounts. Whereas cells expressing the HIV-1 or HIV-2_ROD env gene products were found to undergo fusion with uninfected CD4⁺ cells, no syncytium formation was observed with three CD4⁺ cell lines exposed to the cells expressing the envelope glycoproteins of HIV-2_ST on their surfaces; one CD4⁺ lymphoid cell line (SupT1) exhibited few very small syncytia in the presence of recombinant HIV-2_ST envelope glycoproteins. The failure of the HIV-2_ST envelope glycoprotein to induce cell fusion was not the result of an inhibition by cell-associated CD4, since fusion was also not observed when rVV_ST-infected CD4^- cells were cocultured with CD4⁺ cells. Thus, the HIV-2_ST envelope protein itself is defective in its ability to induce cell fusion. Furthermore, the expression, processing, transport, and surface stability of env products of HIV-2_ST are unlikely to be responsible for its attenuation, suggesting that the molecular interactions between its env products and target cell membranes are significantly altered.