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Previous studies have shown that the gene coding for the Vpu protein of the human immunodeficiency virus type 1 (HIV-1) is 5' to the env gene, is in a different reading frame, and overlaps the env by 90 nucleotides. In this study, we examined the processing of the Env protein as well as the maturation and infectivity of a virus (SHIV Vpenv ) in which a single nucleotide...
Several studies have shown that deletion of the nef gene of simian immunodeficiency virus (SIV) and simian–human immunodeficiency virus (SHIV) results in attenuated viruses. However, studies have not critically examined trafficking of attenuated viruses to the central nervous system (CNS) at early stages after inoculation. In this study, we investigated the colocalization of pathogenic and vpu-negative,...
The Vpu protein of human immunodeficiency virus type 1 (HIV-1) has been reported to enhance virion release from infected cells and to down-regulate the expression of CD4 on infected cells. Previous studies have shown that Vpu and the envelope glycoprotein precursor (gp160) are translated from different reading frames of the same bicistronic messenger RNA (mRNA). In order to assess the effect of the...
Previous studies have shown that passage of nonpathogenic SHIV-4 through a series of macaques results in the selection of variants of the virus that are capable of causing rapid subtotal loss of CD4 + T cells and AIDS within 6–8 months following inoculation into pig-tailed macaques. Using a pathogenic variant of SHIV-4 known as SHIV KU-1bMC33 , we reported that a mutant of this virus...
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 (ΔvpuSHIV KU-1bMC33 ) in which 42 of 82 amino acids of Vpu...
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). We report here on the...
A chimeric simian-human immunodeficiency virus (SHIV-4) containing thetat, rev, vpu,andenvgenes of HIV type 1 (HIV-1) in a genetic background of SIV mac 239 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...
Recently, we developed a highly pathogenic variant of simian–human immunodeficiency virus, SHIV-4 (containing thetat, rev, vpu,andenvof the HXB2 strain of HIV-1 in a genetic background of SIV mac 239), through a series of four bone marrow-bone marrow passages—first in rhesus monkeys and then in pig-tailed macaques [Joaget al. (1996) J. Virol.70, 3189–3197]. Inoculation of pig-tailed macaques...
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