REDUCED VIRAL LOAD AND LACK OF CD4 DEPLETION IN SCID-HU MICE INFECTEDWITH REV-INDEPENDENT CLONES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

The posttranscriptional control element CTE of the simian type D retro virus has been shown to support replication of Rev-Rev-responsive-elem ent (RRE)-deficient molecular clones of human immunodeficiency virus t ype 1 (HIV-1). Upon infection of peripheral blood mononuclear cells in vitro, these CTE-containing Rev-independent viruses that are nef(+) o r nef-minus showed lower replicative capacity and infectivity than the wild-type HIV-1. We studied the effects of Rev-RRE replacement by the CTE on HIV-1 expression with SCID-hu mice. The nef(+) and nef-minus R ev-independent viruses established infection with kinetics slower than that of the nef-minus NL4-3. Most importantly, no depletion of CD4-be aring thymocytes was observed after 6 weeks for mice infected with the se Rev-independent viruses. This is in contrast to the infection with both wild-type and nef-minus viruses, which led to varying depletion o f thymocytes. These data suggest an attenuated phenotype for growth an d cytotoxicity of the Rev-independent HIV-1 clones in SCID-hu mice, in dependent of the presence of Nef. The mutant viruses, which have the e ssential Rev-RRE regulatory system eliminated, display a distinct phen otype not previously observed with HIV mutant viruses having deletions of accessory genes. Therefore, replacement of the Rev-RRE regulatory axis may generate viruses with altered biological properties in vivo.