Human immunodeficiency virus type 1 infection of mature CD3hiCD8+ 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 CD3hiCD4+ and CD3hiCD8+ 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 CD3hiCD8+ 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 CD3hiCD8+ 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.
Lee
S
S
Laboratory of Retrovirus Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Goldstein
H
H
Baseler
M
M
Adelsberger
J
J
Golding
H
H
D000818:Animals; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004279:DNA, Viral / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D011533:Proviruses / Q000235:genetics; D012333:RNA, Messenger; D012367:RNA, Viral; D013950:Thymus Gland / Q000166:cytology / Q000821:virology*; D014158:Transcription, Genetic
D017252:CD3 Complex; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral