HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion.
Homozygosity for the 32 base-pair deletion (Delta32/Delta32) in the CCR5 coreceptor gene is associated with incomplete HIV-1 resistance. Six HIV-1-infected Delta32/Delta32 patients have been reported. We report 2 additional Delta32/Delta32-infected individuals, among 106 seroconverters in a vaccine preparedness study. Like the previous 6, these individuals experienced rapid CD4 decline. However, taken together, the 8 patients have neither uniformly high virus load nor rapid progression to AIDS. We obtained five virus isolates from 1 patient at 5, 6, 7, 10, and 12 months after the estimated time of infection. The earliest isolate exhibits the syncytium-inducing (SI) phenotype and exclusive use of the CXCR4 coreceptor, suggesting acquisition of HIV-1 through this coreceptor. Of the remaining 104 seroconverters, 8 were CCR5-Delta32/+ and 96 were CCR5-+/+. Three CCR5-+/+ seroconverters who showed the uncommon pattern of early SI virus and rapid CD4 decline had uniformly high viral load and more heterogeneous coreceptor usage. These results further support the conclusion that Delta32-mediated resistance is incomplete and is associated with acquisition of exclusively-X4 variants of HIV-1. The pathogenic potential of these viruses may be different from late-stage X4 virus or early X4 virus acquired by individuals with other CCR5 genotypes.
Sheppard
Haynes W
HW
Viral and Rickettsial Disease Laboratory, California Department of Health Services, Richmond, California 94804, USA. hsheppar@dhs.ca.gov
Celum
Connie
C
Michael
Nelson L
NL
O'Brien
Stephen
S
Dean
Michael
M
Carrington
Mary
M
Dondero
Dale
D
Buchbinder
Susan P
SP
D020029:Base Pairing / Q000235:genetics; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015726:Giant Cells / Q000502:physiology*; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D006679:HIV Seropositivity; D015497:HIV-1 / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology*; D020180:Heteroduplex Analysis; D006720:Homozygote; D006801:Humans; D008297:Male; D019713:Receptors, CCR5 / Q000235:genetics*; D019562:Viral Load
D019713:Receptors, CCR5