Identification of two distinct subsets of long-term nonprogressors with divergent viral activity by stromal-derived factor 1 chemokine gene polymorphism analysis.
Stromal-derived factor (SDF)-1, the natural ligand for CXCR4, is present in a common polymorphic variant defined by a G-->A transition in the 3' untranslated region of the gene. In persons infected with human immunodeficiency virus type 1 (HIV-1), the homozygous genotype (SDF1-3'A/3'A) has been postulated to interfere with the appearance of T-tropic syncytium-inducing strains. The polymorphism of SDF1 was correlated with HIV-1 phenotype, plasma viremia, and unspliced and multiply spliced specific transcripts in 158 virologically characterized HIV-1-infected patients (39 recent seroconverters, 75 typical progressors, and 44 AIDS patients) and in 42 HIV-1-infected long-term nonprogressors (LTNPs). Analysis of SDF1 allele distribution revealed that SDF1-3'A/3'A status is associated with low CD4 cell count (P=.0449) but not with a specific HIV-1 phenotype. In LTNPs, SDF1-+/+ condition defined a subset of persons with lower HIV-1 replication than in heterozygous subjects. The low viral activity in SDF1-+/+ LTNPs suggests that other factors play a major role in vivo in determining the course of HIV-1 infection.
Balotta
C
C
Institute of Infectious and Tropical Diseases, L. Sacco Hospital, University of Milan, 20157 Milan, Italy. Claudia.Balotta@unimi.it
Bagnarelli
P
P
Corvasce
S
S
Mazzucchelli
R
R
Colombo
M C
MC
Papagno
L
L
Santambrogio
S
S
Ridolfo
A L
AL
Violin
M
M
Berlusconi
A
A
Velleca
R
R
Facchi
G
G
Moroni
M
M
Clementi
M
M
Galli
M
M
D000328:Adult; D000368:Aged; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D005260:Female; D015726:Giant Cells / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012367:RNA, Viral