CONSTRUCTION AND IN-VITRO PROPERTIES OF HIV-1 MUTANTS WITH DELETIONS IN NONESSENTIAL GENES

Auxiliary genes that are not essential for viral replication in cell c ulture are found in all known lentiviruses. The ''nonessential'' auxil iary genes of HIV-1 are vif, vpr, vpu, and nef. Sequences within the u pstream region of U3 in the LTR are also not required for virus replic ation in cell culture. We constructed a panel of 23 mutants with singl e and combination deletions in these regions in the wild-type HIV-1 in fectious molecular clone NL4-3. Deletion of the vpu, vpr, and nef gene s and the U3 upstream sequence (US), individually or in combinations, did not appreciably alter virus replication in either chimpanzee PBMCs , human PBMCs, or in the B/T cell hybrid line CEMx174. In contrast, de letion of the vif gene dramatically delayed virus replication in all t hree cell types. This collection of HIV-1 deletion mutants will be use ful for elucidating the functions of these genes and for investigating antiviral immunity in animal models.