UNIMPAIRED FUNCTION OF A NATURALLY-OCCURRING C-TERMINALLY TRUNCATED VIF GENE-PRODUCT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

In similar to 10 % of natural human immunodeficiency virus 1 (HIV-1) v if gene populations, sequences of shortened vif open reading frames wi th premature stop codons have been found. Here we report the functiona l analysis of two patient-derived vif genes. Vif45-2 encodes a C termi nally truncated Vif protein of only 173 instead of 192 amino acids and additionally contains several rare amino acid substitutions which are in part shared by vifAG5-5. HIV-1 pNL4-3-derived recombinant A45-2 an d A65-5 virions were fully infectious in H9 cells and human PBMC, both known to be non-permissive for vif-defective HIV-1. Furthermore, A45- 2 virions produced in primary human monocyte-derived macrophages were infectious for MT-4 cells. This study unequivocally demonstrates that the C-terminal region (19 amino acids) of the Vif protein is dispensab le for Vif function in the in vitro cell culture systems employed. Add itionally, we investigated whether the Vif protein might be phosphoryl ated in vivo and obtained no evidence for this.