HIV preferentially infects HIV-specific CD4+ T cells.
HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.
Douek
Daniel C
DC
Vaccine Research Center, NIAID, NIH, Maryland 20892, USA. ddouek@mail.nih.gov
Brenchley
Jason M
JM
Betts
Michael R
MR
Ambrozak
David R
DR
Hill
Brenna J
BJ
Okamoto
Yukari
Y
Casazza
Joseph P
JP
Kuruppu
Janaki
J
Kunstman
Kevin
K
Wolinsky
Steven
S
Grossman
Zvi
Z
Dybul
Mark
M
Oxenius
Annette
A
Price
David A
DA
Connors
Mark
M
Koup
Richard A
RA
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002455:Cell Division; D002478:Cells, Cultured; D004279:DNA, Viral / Q000097:blood; D006678:HIV / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D019562:Viral Load
D019380:Anti-HIV Agents; D004279:DNA, Viral; D007371:Interferon-gamma