HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF MATURE CD3(HI)CD8(+)THYMOCYTES

Although CD4(+) cells are the primary targets of human immunodeficienc y virus type 1 (HIV-1) infection, earlier reports have suggested that intrathymic infection of CD8(+) cells may occur. However, it was uncle ar whether HIV-1-infected CD8(+) thymocytes were truly mature single-p ositive (SP) cells, In the present study, SCID mice implanted with hum an fetal thymus and liver tissues (SCID-hu mice) were infected with th ree primary isolates of HIV-1 and infected thymocytes were analyzed to assess maturational status, After intra-implant or intraperitoneal in jection with HIV-1, thymocytes were sorted by three-color flow cytomet ric 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(+) po pulation), The presence of HIV-1 provirus in the sorted thymocyte popu lations was determined by quantitative PCR, A fraction of mature CD3(h i)CD8(+) thymocytes contained HIV-1 proviral DNA, and evidence of vira l mRNA transcription in these cells,vas demonstrated by in situ hybrid ization. In contrast, when uninfected CD3(hi)CD8(+) thymocytes were co cultured with HIV-1-infected CD4(+) thymocytes, no evidence of product ive HIV-1 infection was detected, Thus, HIV-1 infection of CD8(+) thym ocytes in the SCID-hu mouse does not occur by direct contact with the virus, Rather, cell surface CD4 is required; therefore, precursor cell s are the likely primary target of HIV-1 infection in the thymus, Duri ng ontogeny, some of these infected cells continue their differentiati on into mature CD8(+) SP thymocytes that contain proviral DNA and expr ess viral RNA.