TY - JOUR
T1 - Human immunodeficiency virus type 1 infection of mature CD3(hi)CD8+ thymocytes
AU - Lee, Shirley
AU - Goldstein, Harris
AU - Baseler, Michael
AU - Adelsberger, Joe
AU - Golding, Hana
PY - 1997
Y1 - 1997
N2 - 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 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.
AB - 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 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.
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U2 - 10.1128/jvi.71.9.6671-6676.1997
DO - 10.1128/jvi.71.9.6671-6676.1997
M3 - Article
C2 - 9261389
AN - SCOPUS:0030749208
SN - 0022-538X
VL - 71
SP - 6671
EP - 6676
JO - Journal of virology
JF - Journal of virology
IS - 9
ER -