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Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to the suppression of HIV viremia below the threshold of detection for several years. However, impact of HAART on reconstitution of virus-specific immune responses remains poorly understood. In this study, four macaques were infected with pathogenic SHIV KU . One week postinoculation two of the four animals...
SHIV KU2 replicates to high levels in inoculated macaques and reproducibly causes an acute depletion of CD4 + T cells. We evaluated the ability of treatment with the antiretroviral drug 9-R-(2-phosphonomethoxypropyl)adenine (PMPA; tenofovir), begun 7 days postinoculation, to inhibit viral replication and associated pathogenesis. Highly productive infection (plasma viral RNA > 10...
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...
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...
Twenty macaques were used to evaluate the ability of nonpathogenic SIV mac or nonpathogenic chimeric SIV-HIV (SHIV) to induce protection in macaques against superinfection with a pathogenic variant of SHIV (SHIV KU-1 ) originally containing thetat, rev, vpu,andenvof HIV-1 (strain HXB2) in a genetic background of SIV mac 239. Specifically, three macaques inoculated with molecularly...
Molecularly cloned SIVmac239 is the prototypical SIVmaclymphocyte-tropic virus that replicates productively in lymphocytes but poorly in macrophages. In macaques, the virus causes activation and productive infection of T lymphocytes which invade the central nervous system (CNS) early after infection in the animal. However, infected animals develop immunosuppression and AIDS but rarely overt neurological...
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