1. Rapid CD4+ T-lymphocyte depletion in rhesus monkeys infected with a simian-human immunodeficiency virus expressing the envelope glycoproteins of a primary dual-tropic Ethiopian Clade C HIV type 1 isolate.
- Author
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Cayabyab M, Rohne D, Pollakis G, Mische C, Messele T, Abebe A, Etemad-Moghadam B, Yang P, Henson S, Axthelm M, Goudsmit J, Letvin NL, and Sodroski J
- Subjects
- Amino Acid Sequence, Animals, CD4-Positive T-Lymphocytes immunology, Ethiopia, Gene Products, env genetics, HIV Infections immunology, HIV Infections virology, HIV-1 genetics, Humans, Macaca mulatta, Molecular Sequence Data, Sequence Analysis, DNA, Serial Passage, Simian Acquired Immunodeficiency Syndrome immunology, Simian Acquired Immunodeficiency Syndrome physiopathology, Simian Acquired Immunodeficiency Syndrome virology, Simian Immunodeficiency Virus genetics, Time Factors, CD4-Positive T-Lymphocytes pathology, Gene Products, env metabolism, HIV-1 classification, HIV-1 pathogenicity, Receptors, CCR5 metabolism, Receptors, CXCR4 metabolism, Simian Immunodeficiency Virus pathogenicity
- Abstract
Simian-human immunodeficiency virus (SHIV) chimerae with the envelope glycoproteins of X4 or R5/X4 HIV-1 isolates from clade B can cause rapid and severe CD4(+) T cell depletion and AIDS-like illness in infected monkeys. We created a SHIV (SHIV-MCGP1.3) expressing the envelope glycoproteins of a primary R5/X4, clade C HIV-1 isolate. Infection of a rhesus monkey with SHIV-MCGP1.3 resulted in a low level of viremia and no significant alteration in CD4(+) T-lymphocyte counts. However, serial intravenous passage of the virus resulted in the emergence of SHIV-MCGP1.3 variants that replicated efficiently and caused profound CD4(+) T cell depletion during the acute phase of infection. The CD4(+) T cell counts in the infected monkeys gradually returned to normal, and the animals remained healthy. The ability to cause rapid and profound loss of CD4(+) T lymphocytes in vivo is a property shared by passaged, CXCR4-using SHIVs, irrespective of the clade of origin of the HIV-1 envelope glycoproteins.
- Published
- 2004
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