CXCR4 and CCR5 genetic polymorphisms in long-term nonprogressive human immunodeficiency virus infection: lack of association with mutations other than CCR5-Delta32.
Polymorphisms in the coding sequences of CCR5 and CXCR4 were studied in a group of human immunodeficiency virus (HIV)-infected long-term nonprogressors. Two different point mutations were found in the CXCR4 coding sequence. One of these CXCR4 mutations was silent, and each was unique to two nonprogressors. The well-described 32-bp deletion within the CCR5 coding sequence (CCR5-Delta32) was found in 4 of 13 nonprogressors, and 12 different point mutations were found scattered over the CCR5 coding sequence from 8 nonprogressors. Most of the mutations created either silent or conservative changes in the predicted amino acid sequence: only one of these mutations was found in more than a single nonprogressor. All nonsilent mutations were tested in an HIV envelope-dependent fusion assay, and all functioned comparably to wild-type controls. Polymorphisms in the CXCR4 and CCR5 coding sequences other than CCR5-Delta32 do not appear to play a dominant mechanistic role in nonprogression among HIV-infected individuals.
Cohen
O J
OJ
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-1876, USA. OCohen@nih.gov
Paolucci
S
S
Bende
S M
SM
Daucher
M
M
Moriuchi
H
H
Moriuchi
M
M
Cicala
C
C
Davey
R T
RT
Baird
B
B
Fauci
A S
AS
D005260:Female; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000235:genetics*
D019713:Receptors, CCR5; D019718:Receptors, CXCR4