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

Genotypic and phenotypic characterization of viral isolates from HIV-1 subtype C-infected children with slow and rapid disease progression
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DOI:
10.1089/aid.2006.22.458
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发表时间:
2006-05-01
影响因子:
1.5
通讯作者:
Morris, Lynn
Morris, Lynn
中科院分区:
医学4区
文献类型:
--
作者:
Choge, Isaac;Cilliers, Tonie;Morris, Lynn

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分析了从南非40例围产期感染儿童中获得的HIV-1分离株的基因型和生物学表型。这包括15名有艾滋病毒相关症状的婴儿,其中大多数在出生后2年内死亡(快速进展者),以及25名存活4至9年的儿童,具有不同的疾病体征(缓慢进展者)。异源双链迁移率测定和序列分析证实,在env和gag区域内,所有分离株均为HIV-1 C亚型。来自15个快速进展者中的14个的病毒分离株使用CCR 5辅助受体,而1个(02 ZARP 1)使用CXCR 4和CCR 5辅助受体两者。在25个缓慢进展者中,22个分离株仅使用CCR 5,2个分离株仅使用CXCR 4,1个分离株同时使用CCR 5和CXCR 4。两名携带CXCR 4病毒的进展缓慢的儿童患有艾滋病。所有四种使用CXCR 4的病毒在V3区都有基因型变化,先前显示与CXCR 4的使用相关。这项横断面研究表明,来自快速和缓慢进展的围产期感染儿童的HIV-1 C亚型病毒主要使用CCR 5。与成人相似,CXCR 4的使用在儿科感染的HIV-1 C亚型分离株中并不常见。
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.