Genotypic and phenotypic characterization of viral isolates from HIV-1 subtype C-infected children with slow and rapid disease progression.
The genotypes and biological phenotypes of HIV-1 isolates obtained from 40 perinatally infected children in South Africa were analyzed. This included 15 infants who had HIV-related symptoms, most of whom died within 2 years of birth (rapid progressors), and 25 children who survived between 4 and 9 years with varying signs of disease (slow progressors). Heteroduplex mobility assays and sequence analysis confirmed that within the env and gag regions, all isolates were HIV-1 subtype C. Viral isolates from 14 of the 15 rapid progressors used the CCR5 coreceptor, whereas 1 (02ZARP1) used both the CXCR4 and CCR5 coreceptors. Among the 25 slow progressors, 22 isolates used CCR5 only, 2 used CXCR4 only, and 1 used both CCR5 and CXCR4. Two of the slow-progressing children who harbored CXCR4-using viruses had AIDS. All four CXCR4-using viruses had genotypic changes in the V3 region previously shown to be associated with CXCR4 usage. This cross-sectional study shows that HIV-1 subtype C viruses from both rapid- and slow-progressing perinatally infected children used predominantly CCR5. Similar to adults, CXCR4 usage was uncommon among HIV-1 subtype C isolates from pediatric infections.
Choge
Isaac
I
AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa.
Cilliers
Tonie
T
Walker
Polly
P
Taylor
Natasha
N
Phoswa
Mary
M
Meyers
Tammy
T
Viljoen
Johannes
J
Violari
Avy
A
Gray
Glenda
G
Moore
Penny L
PL
Papathanosopoulos
Maria
M
Morris
Lynn
L
D000163:Acquired Immunodeficiency Syndrome / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D015752:Genes, env; D015750:Genes, gag; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics*; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013997:Time Factors
D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4