Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy.
We have identified a subset of CD56(+)CD3(-) human natural killer (NK) cells that express CD4 and the HIV coreceptors CCR5 and CXCR4. These cells can be productively infected in vitro by both CCR5- and CXCR4-using molecular clones of HIV-1 in a CD4-dependent manner. Analysis of HIV-infected persons showed that viral DNA is present in purified NK cells, and virus could be rescued from these cells after in vitro cultivation. Longitudinal analysis of the HIV-1 DNA levels in NK cells from patients after 1-2 years of highly active antiretroviral therapy indicated that NK cells remain persistently infected and account for a substantial amount of the viral DNA in peripheral blood mononuclear cells. These results demonstrate that a subset of non-T cells with NK markers are persistently infected and suggest that HIV infection of NK cells is important for virus persistence. The properties of the virus reservoir in these cells should be considered in attempts to further optimize antiretroviral therapies.
Valentin
Antonio
A
Human Retrovirus Section, Basic Research Laboratory, National Cancer Institute, Frederick, MD 21702, USA.
Rosati
Margherita
M
Patenaude
Daniel J
DJ
Hatzakis
Angelos
A
Kostrikis
Leondios G
LG
Lazanas
Marios
M
Wyvill
Kathleen M
KM
Yarchoan
Robert
R
Pavlakis
George N
GN
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D019002:CD56 Antigen; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology*; D016131:Lymphocyte Subsets; D019713:Receptors, CCR5 / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D019002:CD56 Antigen; D019713:Receptors, CCR5; D019718:Receptors, CXCR4