Regulation of HIV replication by a host transcription factor NFκB

Abstract

On the basis of sequence homology, four distinct groups of primate immunodeficiency viruses are now recognized. These viruses possess a number of auxiliary genes not found in other retroviruses, i.e., tat, rev, nef, vif, vpr, vpu, and vpx genes. The general conservation of these accessory genes, within a group and in some cases among all four primate immunodeficiency viruses, argl~es for an important functional role in the virus life cycle. These genes can be further characterized as essential and non-essential. Non-essential genes include nef, vif, vpr, vpu, and vpx. Human immunodeficiency virus type I (HIV-I), a magor causative agent of human AIDS, contains these auxiliary genes except for the vpx. Although the biology and molecular biology of HIV-I have been extensively studied, molecular bases for actions of the non-essential gene products, which are unique to the primate lentivirus group, are not fully understood yet. Recent studies have d~monstrated that most of the non-essential gene products act at various stages of virus life cycle in a cell-specific manner. We also have shown t_hat some gag gene mutants can replicate in some specific cell lines. The observed cell-specificity is critical for our understanding of the virology of HIV. In this report, to study functions of various HIV proteins, a large number of mutants were constructed, and bilogically and biochemically characterized. Growth kinetics of mutant viruses in several cell lines and primary blood cell cultures were determined, and defective steps in the viral life cycle of the mutants were monitored by our single-round replication assays. Target genes for study include gag, nef, vif, vpr, vpu, and vpx. We s~mmarize our new data regarding cell-dependent requirement of various HIV proteins for viral replication.