Construction and In Vitro Properties of HIV-1 Mutants with Deletions in "Nonessential" Genes

Authors:
  • DRDean A. Regier
    Dean A. Regier
  • RDRonald C. Desrosiers
    Ronald C. Desrosiers
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Abstract
Auxiliary genes that are not essential for viral replication in cell culture are found in all known lentiviruses. The "nonessential" auxiliary genes of HIV-1 are vif, vpr, vpu , and nef . Sequences within the upstream region of U3 in the LTR are also not required for virus replication in cell culture. We constructed a panel of 23 mutants with single and combination deletions in these regions in the wild-type HIV-1 infectious molecular clone NL4-3. Deletion of the vpu, vpr , and nef genes 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, deletion of the vif gene dramatically delayed virus replication in all three cell types. This collection of HIV-1 deletion mutants will be useful for elucidating the functions of these genes and for investigating antiviral immunity in animal models.

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