Impact of Delta 32-CCR5 heterozygosity on HIV-1 genetic evolution and variability--a study of 4 individuals infected with closely related HIV-1 strains.
A cluster of four patients acutely infected with a genetically almost identical virus, allowed us to investigate genetic variability and disease progression in early HIV-1 infection with minimal interference of virus specific factors. Two of the patients were heterozygous for the 32-bp deletion in the CCR5 coreceptor gene. Both showed a slower disease progression with lower viral load levels and a reduced rate of genetic evolution compared to the patients with normal CCR5 alleles. During 3 years of treatment-free follow-up, the mean pairwise genetic distance increased with 1.45% and 1.58% in the two patients with a 32-bp deletion allele compared to 3.05% and 3.57% in the two patients with normal CCR5 alleles. The observed relation between slower disease progression and a reduced evolutionary rate illustrates the influence of the virus replicative capacity, here most possibly hampered by the CCR5 heterozygosity in two of the four individuals, on the genetic evolution of the virus in the host.
Chalmet
Kristen
K
AIDS Reference Laboratory, Ghent University and Ghent University Hospital, De Pintelaan, 185-Block A, B-9000 Gent, Belgium. Kristen.Chalmet@ugent.be
Van Wanzeele
Filip
F
Demecheleer
Els
E
Dauwe
Kenny
K
Pelgrom
Jolanda
J
Van Der Gucht
Bea
B
Vogelaers
Dirk
D
Plum
Jean
J
Stuyver
Lieven
L
Vandekerckhove
Linos
L
Verhofstede
Chris
C
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D019143:Evolution, Molecular; D015752:Genes, env; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion
D017931:DNA Primers; D012367:RNA, Viral; D019713:Receptors, CCR5