HIV type 1 persistence in CD4- /CD8- double negative T cells from patients on antiretroviral therapy.
The establishment of reservoirs of latently infected cells is thought to contribute to the persistence of HIV-1 infection in the host. Studies so far have mainly focused on the long-lived reservoir of HIV-infected resting CD4+ T cells. A discrete population of HIV-infected CD4-/CD8- double negative (DN) T cells has recently been shown to exist and may also play a role in HIV-1 persistence. DN T cells are CD3 positive, either TCRalphabeta or TCRgammadelta positive, but lack both CD4 and CD8 surface markers. We developed a novel, magnetic bead column-based cell fractionation procedure for isolating >99% pure DN T cells. CD4+, CD8+, and DN T cells were purified from 23 samples of a cohort of 18 HIV-1-infected patients. Each cell fraction was analyzed for levels of total and integrated HIV-1 DNA. A correlation was observed between the presence of HIV-1 DNA in the DN T cell fraction and plasma viral load (VL). Using a micrococulture technique, we saw an initial release of virus from DN T cells of a patient with high VL. Analysis of env and nef sequence data suggested that the HIV-1 present in CD4+ and DN T cells originated from a common infecting strain. Different from the published literature, we have demonstrated the presence of HIV-1 DNA in DN T cells only in patients who are experiencing HAART failure. While these cells may have a limited role in viral persistence in high VL patients, our results suggest DN T cells are unlikely to be a major reservoir in patients on HAART with clinically undetectable plasma viral RNA.
Cheney
Kelly M
KM
Australian Centre for Hepatitis and HIV Virology Research, Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide SA, Australia 5000.
Kumar
Raman
R
Purins
Adrian
A
Mundy
Linda
L
Ferguson
Wendy
W
Shaw
David
D
Burrell
Christopher J
CJ
Li
Peng
P
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D019562:Viral Load
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D016827:CD8 Antigens; D012367:RNA, Viral