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

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... ational status. After intraimplant 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 was 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.