Genotypic and phenotypic characterization of viral isolates from HIV-1 subtype C-infected children with slow and rapid disease progression

• Published in: AIDS research and human retroviruses Vol. 22; no. 5; p. 458
• Main Authors: Choge, Isaac, Cilliers, Tonie, Walker, Polly, Taylor, Natasha, Phoswa, Mary, Meyers, Tammy, Viljoen, Johannes, Violari, Avy, Gray, Glenda, Moore, Penny L, Papathanosopoulos, Maria, Morris, Lynn
• Format: Journal Article
• Language: English
• Published: United States 01.05.2006
• Subjects: Acquired Immunodeficiency Syndrome - mortality; Child; Child, Preschool; Cross-Sectional Studies; Disease Progression; Female; Genes, env; Genes, gag; Genotype; HIV Infections - virology; HIV-1 - classification; HIV-1 - genetics; HIV-1 - isolation & purification; Humans; Infant; Male; Molecular Sequence Data; Phenotype; Phylogeny; Receptors, CCR5 - metabolism; Receptors, CXCR4 - metabolism; RNA, Viral - genetics; Sequence Analysis, DNA; Time Factors
• ISSN: 0889-2229; 1931-8405
• DOI: 10.1089/aid.2006.22.458

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.