The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression.
Entry of human immunodeficiency virus type 1 (HIV-1) into target cells requires both CD4 (ref. 1, 2) and one of a growing number of G-protein-coupled seven-transmembrane receptors. Viruses predominantly use one, or occasionally both, of the major co-receptors CCR5 or CXCR4, although other receptors, including CCR2B and CCR3, function as minor co-receptors. CCR3 appears critical in central nervous system infection. A 32-base pair inactivating deletion in CCR5 (delta 32) common to Northern European populations has been associated with reduced, but not absolute, HIV-1 transmission risk and delayed disease progression. A more commonly distributed transition causing a valine to isoleucine switch in transmembrane domain I of CCR2B (64I) with unknown functional consequences was recently shown to delay disease progression but not reduce infection risk. Although we confirm the lack of association of CCR2B 64I with transmission, we cannot confirm the association with delayed progression. Although subjects with CCR5 delta 32 defects had significantly reduced median viral load at study entry, providing a plausible explanation for the association with delayed progression, this association was not seen with CCR2B 64I. Further studies are needed to define the role of CCR2B64I in HIV pathogenesis.
Michael
N L
NL
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850, USA.
Louie
L G
LG
Rohrbaugh
A L
AL
Schultz
K A
KA
Dayhoff
D E
DE
Wang
C E
CE
Sheppard
H W
HW
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000401:mortality / Q000635:transmission*; D017931:DNA Primers; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000097:blood; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D015996:Survival Rate; D013997:Time Factors
C515334:CCR2 protein, human; D017931:DNA Primers; D012367:RNA, Viral; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine