Effect of nef alleles on replication of human immunodeficiency virus type 1.

The effect of multiple alleles of nef of the human immunodeficiency virus type 1 (HIV-1) on virus replication was examined. Nef alleles used include some derived from isolates of virus passaged in tissue culture as well as others obtained by direct cloning of viral DNA from tissues of infected patients. The effect of nef on virus replication was evaluated in the context of a derivative of the HXB2 provirus shown previously to require nef for rapid growth in CD4+ human T cell lines and in primary peripheral blood mononuclear cells. The results of the experiments show that in this genetic context all of the studied viruses carrying nef alleles that express stable Nef proteins replicate more rapidly than do their, otherwise isogenic, nef-defective counterparts. Two of the nef alleles derived from primary tissues produce unstable proteins. These studies demonstrate that naturally occurring nef alleles can increase the rate of virus replication in both primary peripheral blood mononuclear cells and in a CD4+ T cell line. The results also demonstrate that functional variation exists among naturally occurring nef alleles.