Human Immunodeficiency Virus Type 1 Infection of Mature Cd3(Hi)Cd8(+) Thymocytes

Although CD4(+) cells are the primary targets of human immunodeficiency virus type 1 (HIV-1) infection, earlier reports have suggested that intrathymic infection of CD8(+) cells may occur. However, it was unclear whether HIV-1-infected CD8(+) thymocytes were truly mature single-positive (SP) cells, In the present study, SCID mice implanted with human fetal thymus and liver tissues (SCID-hu mice) were infected with three primary isolates of HIV-1 and infected thymocytes were analyzed to assess maturational status, After intra-implant or intraperitoneal injection with HIV-1, thymocytes were sorted by three-color flow cytometric analysis into mature populations of CD3(hi)CD4(+) and CD3(hi)CD8(+) SP cells of >99% purity (<0.3% CD4-containing cells in the CD8(+) population), The presence of HIV-1 provirus in the sorted thymocyte populations was determined by quantitative PCR, A fraction of mature CD3(hi)CD8(+) thymocytes contained HIV-1 proviral DNA, and evidence of viral mRNA transcription in these cells,vas demonstrated by in situ hybridization. In contrast, when uninfected CD3(hi)CD8(+) thymocytes were cocultured with HIV-1-infected CD4(+) thymocytes, no evidence of productive HIV-1 infection was detected, Thus, HIV-1 infection of CD8(+) thymocytes in the SCID-hu mouse does not occur by direct contact with the virus, Rather, cell surface CD4 is required; therefore, precursor cells are the likely primary target of HIV-1 infection in the thymus, During ontogeny, some of these infected cells continue their differentiation into mature CD8(+) SP thymocytes that contain proviral DNA and express viral RNA. [References: 32]

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