Human immunodeficiency virus type 1 can establish latent infection in resting CD4+ T cells in the absence of activating stimuli.
Resting CD4(+) T cells are the best-defined reservoir of latent human immunodeficiency virus type 1 (HIV-1) infection, but how the reservoir is formed is unclear. Understanding how the reservoir of latently infected cells forms is critical because it is a major barrier to curing HIV infection. The system described here may provide an in vitro model of latent HIV-1 infection in resting CD4(+) T cells. We demonstrated that HIV-1 integrates into the genomes of in vitro-inoculated resting CD4(+) T cells that have not received activating stimuli and have not entered cell cycle stage G(1b). A percentage of the resting CD4(+) T cells that contain integrated DNA produce virus upon stimulation, i.e., are latently infected. Our results show that latent HIV-1 infection occurs in unstimulated resting CD4(+) T cells and suggest a new route for HIV-1 reservoir formation.
Swiggard
William J
WJ
Department of Medicine, University of Pennsylvania, USA.
Baytop
Clifford
C
Yu
Jianqing J
JJ
Dai
Jihong
J
Li
Chuanzhao
C
Schretzenmair
Richard
R
Theodosopoulos
Ted
T
O'Doherty
Una
U
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002453:Cell Cycle; D002460:Cell Line; D004197:Disease Reservoirs; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D011533:Proviruses / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D016662:Virus Integration; D017735:Virus Latency
D015703:Antigens, CD