Comparison of Vpu sequences from diverse geographical isolates of HIV type 1 identifies the presence of highly variable domains, additional invariant amino acids, and a signature sequence motif common to subtype C isolates.

We compared the Vpu sequences from 101 strains of HIV-1 isolated from diverse geographical regions and various subtypes in order to identify regions of high variability, and those amino acid residues that were highly conserved or invariant. In addition to the highly conserved casein kinase II (CKII) phosphorylation sites, our analysis identified additional invariant residues in the transmembrane domain and in the first and second alpha-helical domains. Our analysis revealed that all subtype C sequences had a conserved LRLL motif at the C terminus that was also found in A/C intersubtype recombinants.

A molecular clone of simian-human immunodeficiency virus (DeltavpuSHIV(KU-1bMC33)) with a truncated, non-membrane-bound vpu results in rapid CD4(+) T cell loss and neuro-AIDS in pig-tailed macaques.

We report on the role of vpu in the pathogenesis of a molecularly cloned simian-human immunodeficiency virus (SHIV(KU-1bMC33)), in which the tat, rev, vpu, env, and nef genes derived from the uncloned SHIV(KU-1b) virus were inserted into the genetic background of parental nonpathogenic SHIV-4. A mutant was constructed (DeltavpuSHIV(KU-1bMC33)) in which 42 of 82 amino acids of Vpu were deleted. Phase partitioning studies revealed that the truncated Vpu was not an integral membrane protein, and pulse-chase culture studies revealed that cells inoculated with DeltavpuSHIV(KU-1bMC33) released viral p27 into the culture medium with slightly reduced kinetics compared with cultures inoculated with SHIV(KU-1bMC33).

Derivation and biological characterization of a molecular clone of SHIV(KU-2) that causes AIDS, neurological disease, and renal disease in rhesus macaques.

Previously, we described the derivation of a pathogenic strain of simian-human immunodeficiency virus (SHIV(KU-2)) consisting of the tat, rev, vpu, and env genes of HIV-1 (strain HXB2) in a genetic background of SIV(mac)239 that causes AIDS and productive infection of the CNS in rhesus macaques (Macca mulatta) (Raghavan et al., 1997, Brain Pathol. 7, 851-861).

Characterization of a neutralization-escape variant of SHIVKU-1, a virus that causes acquired immune deficiency syndrome in pig-tailed macaques.

A chimeric simian-human immunodeficiency virus (SHIV-4) containing the tat, rev, vpu, and env genes of HIV type 1 (HIV-1) in a genetic background of SIVmac239 was used to develop an animal model in which a primate lentivirus expressing the HIV-1 envelope glycoprotein caused acquired immune deficiency syndrome (AIDS) in macaques. An SHIV-infected pig-tailed macaque that died from AIDS at 24 weeks postinoculation experienced two waves of viremia: one extending from weeks 2-8 and the second extending from week 18 until death. Virus (SHIVKU-1) isolated during the first wave was neutralized by antibodies appearing at the end of the first viremic phase, but the virus (SHIVKU-1b) isolated during the second viremic phase was not neutralized by these antibodies.

Chronology of genetic changes in the vpu, env, and Nef genes of chimeric simian-human immunodeficiency virus (strain HXB2) during acquisition of virulence for pig-tailed macaques.

Recently, we developed a highly pathogenic variant of simian-human immunodeficiency virus, SHIV-4 (containing the tat, rev, vpu, and env of the HXB2 strain of HIV-1 in a genetic background of SIVmac239), through a series of four bone marrow-bone marrow passages-first in rhesus monkeys and then in pig-tailed macaques [Joag et al. (1996) J. Virol.