Productive human immunodeficiency virus type 1 infection in peripheral blood predominantly takes place in CD4/CD8 double-negative T lymphocytes.
Human immunodeficiency virus type 1 (HIV-1) transcription is subject to substantial fluctuation during the viral life cycle. Due to the low frequencies of HIV-1-infected cells, and because latently and productively infected cells collocate in vivo, little quantitative knowledge has been attained about the range of in vivo HIV-1 transcription in peripheral blood mononuclear cells (PBMC). By combining cell sorting, terminal dilution of intact cells, and highly sensitive, patient-specific PCR assays, we divided PBMC obtained from HIV-1-infected patients according to their degree of viral transcription activity and their cellular phenotype. Regardless of a patient's treatment status, the bulk of infected cells exhibited a CD4+ phenotype but transcribed HIV-1 provirus at low levels, presumably insufficient for virion production. Furthermore, the expression of activation markers on the surface of these CD4+ T lymphocytes showed little or no association with enhancement of viral transcription. In contrast, HIV-infected T lymphocytes of a CD4-/CD8- phenotype, occurring exclusively in untreated patients, exhibited elevated viral transcription rates. This cell type harbored a substantial proportion of all HIV RNA+ cells and intracellular viral RNAs and the majority of cell-associated virus particles. In conjunction with the observation that the HIV quasispecies in CD4+ and CD4-)/CD8- T cells were phylogenetically closely related, these findings provide evidence that CD4 expression is downmodulated during the transition to productive infection in vivo. The abundance of viral RNA in CD4-/CD8- T cells from viremic patients and the almost complete absence of viral DNA and RNA in this cell type during antiretroviral treatment identify HIV+ CD4-/CD8 T cells as the major cell type harboring productive infection in peripheral blood.
Kaiser
Philipp
P
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich Rämistrasse, 100 8091 Zürich, Switzerland.
Joos
Beda
B
Niederöst
Barbara
B
Weber
Rainer
R
Günthard
Huldrych F
HF
Fischer
Marek
M
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D004279:DNA, Viral / Q000276:immunology / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011533:Proviruses / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D014766:Viremia / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000276:immunology / Q000378:metabolism; D017735:Virus Latency / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D004279:DNA, Viral; D012367:RNA, Viral