Novel tetrameric tip motifs (APGK and VPGK) in the V3 loop of HIV type 1 envelope sequences in blood and brain from two injection drug users in Miami, Florida

Genetic variability is the hallmark of the human immunodeficiency virus (HIV-1), particularly in the envelope (env) gene. This gene encodes the viral surface glycoprotein (gp120) and transmembrane protein (gp41). The gp120 coding sequence includes five hypervariable domains (V1 to V5) interspersed among conserved regions. The "third" hypervariable domain (V3 loop) contains determinants that mediate antibody neutralization, viral tropism, and syncytium induction. The tetrameric tip of the V3 loop contains a tetrapeptide sequence motif that is the major binding site for type-specific neutralizing antibodies and cytotoxic T lymphocytes. Sixty tetrameric tip motifs have been identified among the HIV-1 subtypes. The variation of the motifs for each HIV-1 subtype may have important implications for the epidemiology of AIDS and vaccine development. Worldwide, GPGQ is the most common tetrameric tip motif in the V3 loop among all HIV-1 subtypes, whereas GPGR predominates in the B subtype (66%) found in the Americas and Africa. We have previously identified two novel V3 loop tetrameric tip motifs, HPGR and QPGR, in blood-, and cerebrospinal fluid (CSF)-, and brain-derived B-subtype HIV-1 sequences from an injection drug user (IDU) who died of AIDS (February 2, 1994) in Miami, Florida. In the present study, we report two additional novel tetrameric tip motifs, APGK and VPGK, in the V3 loop of B-subtype HIV-1 envelope sequences isolated from blood and brain, respectively, from two IDUs with AIDS in Miami, Florida.