SIV (HU) was isolated from a researcher who had seroconverted to HIW-2/SIV while working with SIV. The researcher remains asymptomatic after six years of seroconversion, with evidence of extremely low proviral loads, and low yet stable antibody titers. Sequence analysis of LTR, vpr, env and nef regions Of SIV (HU) show it closest (96-98% homology) to SIV (B670), a sooty mangabey strain with which the researcher has primarily worked. Sequences of LTR, vpr, and env revealed no abnormalities of obvious functional significance. In contrast, the nef sequence showed a 4 base deletion, a downstream premature stop codon, and a predicted truncation at amino acid 175. Nef sequence of SIV (B670) predicted a full-length protein. Experimental infection of three macaques with SIV (HU) and three other macaques with SIV (B670), resulted in seroconversion in all six animals. All three SIV (B670) animals died of AIDS-related illnesses at 8.5 and 18 months post inoculation (pi). In contrast, all three SIV (HU)-infected monkeys remain healthy at 24 month pi, show evidence of lower viral loads and antibody titers when compared with the SIV (B670)-animals, and maintain nef truncation. These results provide additional evidence for the role of intact nef in the pathogenicity of SIV in macaques, and extend our knowledge on the role of nef in SIV attenuation in humans.

Animal Genes, env *Genes, nef Genes, vpr Human Macaca Repetitive Sequences, Nucleic Acid SIV/*GENETICS/PATHOGENICITY Simian Acquired Immunodeficiency Syndrome/*GENETICS Virulence/GENETICS ABSTRACT

www.aegis.org