Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 02_AG (CRF02_AG) has a higher in vitro replicative capacity than its parental subtypes A and G
Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 02_AG (CRF02_AG) has a higher in vitro replicative capacity than its parental subtypes A and G
复制标题
DOI：
10.1002/jmv.20572
复制
发表时间：
2006-05-01
影响因子：
12.7
通讯作者：
Nyambi, PN
中科院分区：
文献类型：
--
作者：
Konings, FAJ;Burda, ST;Nyambi, PN
人类免疫缺陷病毒1型（HIV - 1）循环重组形式（CRF）02_AG是喀麦隆的主要亚型，甚至比其亲本亚型A和G更为流行。一个需要解决的重要问题是，HIV - 1感染中的重组是否会导致具有生物学优势的病毒出现。对13株R5嗜性的原发性HIV - 1分离株在外周血单个核细胞（PBMC）中的复制能力进行了研究，其中包括5株CRF02_AG、4株亚型A和4株亚型G病毒。HIV - 1亚型的确定是通过对全长基因组进行系统发育分析，或者对gag、pro、pol和env基因的片段组合进行分析，然后进行重组断点分析。所有病毒在PBMC上培养11天，并对培养上清液进行逆转录酶（RT）活性和p24产生量的分析。在感染后第11天，CRF02_AG毒株的RT活性比亲本亚型A和G高1.4 - 1.9倍，并且p24产生量达到显著更高的水平。此外，通过p24产生量衡量的复制速率，CRF02_AG毒株比亚型A和G高1.4倍。这项研究表明，导致CRF02_AG的重组事件产生了一种比其亲本具有更好复制能力的变体。这种适应性可能有助于HIV - 1 CRF02_AG更广泛的传播，从而导致其在中西非占主导地位，相比之下其亲本亚型A和G的流行率较低。（c）2006威利 - 利斯公司
Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 02(-)AG is the predominant subtype in Cameroon, even more prevalent than the parental subtypes A and G. An important question that needs to be addressed is whether recombination in HIV-1 infection can lead to the emergence of viruses with biological advantages. The replicative capacity was investigated in peripheral blood mononuclear. cells (PBMCs) of 13 R5-tropic primary HIV-1 isolates, including 5 CRF02(-)AG, 4 subtype A, and 4 subtype G viruses. HIV-1 subtype identity was defined by phylogeny either of the full-length genome or analysis of a combination of segments of the gag, pro, pol, and envgenes followed by recombination breakpoint analysis. All viruses were grown on PBMCs for 11 days and culture supernatant was analyzed for reverse transcriptase (RT) activity and p24 production. On day 11 post-infection, CRF02(-)AG strains had a 1.4-1.9 times higher RT activity and reached a significantly higher level of p24 production than the parental subtypes A and G. Furthermore, the replication rate as measured by p24 production was 1.4 times higher for CRF02(-)AG strains compared to the subtypes A and G. This study suggests that the recombination event that led to CRF02_AG resulted in a variant with a better replicative capacity than its progenitors. This adaptation could contribute to the broader spread of HIV-1 CRF02_AG leading to its predominance in West Central Africa compared to the lower prevalence of its parental subtypes A and G. (c) 2006 Wiley-Liss, Inc.