Reduced prevalence of the CCR5 delta32 heterozygous genotype in human immunodeficiency virus-infected individuals with AIDS dementia complex.
Heterozygosity for a 32-bp deletion in the CCR5 gene (CCR5 Delta32), which encodes the coreceptor for macrophage-tropic non-syncytium-inducing (NSI) human immunodeficiency virus type 1 (HIV-1) variants, results in a lower CCR5 expression and reduced NSI HIV-1 replication. Because infection of macrophages and microglial cells by NSI HIV-1 is considered to be instrumental for the development of AIDS dementia complex (ADC), we studied whether the CCR5 Delta32 heterozygous genotype correlated with a reduced frequency of ADC. Two (4.1%) of 49 patients with ADC versus 27 (14. 5%) of 186 AIDS patients without ADC were heterozygous for CCR5 Delta32 (P=.05). In contrast, a point mutation in the first transmembrane domain of CCR2 (CCR2 64I) did not show this protective effect (P=.57). The reduced prevalence of the CCR5 Delta32 allele among patients with ADC may indicate a reduced or absent reservoir of macrophage-tropic NSI HIV-1 in the brain of CCR5 Delta32 heterozygotes.
van Rij
R P
RP
Department of Clinical Viro-Immunology, CLB, and the Laboratory of Experimental and Clinical Immunology of the University of Amsterdam, The Netherlands.
Portegies
P
P
Hallaby
T
T
Lange
J M
JM
Visser
J
J
de Roda Husman
A M
AM
van 't Wout
A B
AB
Schuitemaker
H
H
D015526:AIDS Dementia Complex / Q000235:genetics* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology; D001921:Brain / Q000821:virology; D016022:Case-Control Studies; D005838:Genotype; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008264:Macrophages / Q000821:virology; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion; D014779:Virus Replication
D019713:Receptors, CCR5