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

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.