Rapid and irreversible CD4(+) T-cell depletion induced by the highly pathogenic simian/human immunodeficiency virus SHIVDH12R is systemic and synchronous

Highly pathogenic simian/human immunodeficiency virus chimeric viruses are known to induce a rapid, irreversible depletion of CD4(+) T lymphocytes in the peripheral blood of acutely infected macaque monkeys. To more fully ass ess the systemic effects of this primary virus infection, specimens were co llected serially between days 3 and 21 postinfection from variety of lympho id tissues (lymph nodes, thymus, and spleen) and gastrointestinal tract and examined by DNA and RNA PCR, in situ hybridization, and immunohistochemica l assays. In addition, the lymphoid tissues were evaluated by fluorescence- activated cell sorting. Virus infection was initially detected by DNA PCR o n day 3 postinfection in lymph node samples and peaked on day 10 in the T-l ymphocyte-rich areas of this tissue. CD4(+) T-cell levels remained stable t hrough day 10 in several lymphoid tissue specimens examined but fell precip itously between days 10 and 21. In situ terminal deoxynucleotidyl-transfera se-mediated dUTP-biotin nick end labeling (TUNEL) assays revealed the accum ulation of apoptotic cells during the second week of infection in both lymp h nodes and thymus, which colocalized, to a large extent, to sites of both virus replication and CD4(+) T-lymphocyte loss.