CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms.
Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.
Dolan
Matthew J
MJ
Infectious Disease Clinical Research Program, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA. mdolan@hjf.org
Kulkarni
Hemant
H
Camargo
Jose F
JF
He
Weijing
W
Smith
Alison
A
Anaya
Juan-Manuel
JM
Miura
Toshiyuki
T
Hecht
Frederick M
FM
Mamtani
Manju
M
Pereyra
Florencia
F
Marconi
Vincent
V
Mangano
Andrea
A
Sen
Luisa
L
Bologna
Rosa
R
Clark
Robert A
RA
Anderson
Stephanie A
SA
Delmar
Judith
J
O'Connell
Robert J
RJ
Lloyd
Andrew
A
Martin
Jeffrey
J
Ahuja
Seema S
SS
Agan
Brian K
BK
Walker
Bruce D
BD
Deeks
Steven G
SG
Ahuja
Sunil K
SK
D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology*; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D019713:Receptors, CCR5 / Q000502:physiology*; D019562:Viral Load
C492767:CCL3L1 protein, human; D019742:Chemokines, CC; D019713:Receptors, CCR5