Harris Matthew E, Maayan Shlomo, Kim Bohye, Zeira Michael, Ferrari Guido, Birx Deborah L, McCutchan Francine E
Walter Reed Army Institute of Research, Washington, D.C., USA.
AIDS Res Hum Retroviruses. 2003 Dec;19(12):1125-33. doi: 10.1089/088922203771881220.
The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. One approach to minimize genetic diversity in the evaluation of HIV-1 vaccines is to match the vaccine sequence to the predominant subtype in a vaccine cohort. Over two million Ethiopians are infected with HIV-1, and the predominant subtype is thought to be subtype C. Understanding the phylogenetic relationships between sequences from Ethiopia and within subtype C can help decide what sequence(s) should comprise a candidate vaccine. To that end, nearly full genome sequencing was used to characterize HIV-1 from volunteers who emigrated from Ethiopia. DNA extracted from peripheral blood mononuclear cells (PMBC) was amplified using primers in the long terminal repeats to generate nearly full-length genomes. Amplicons were directly sequenced with dye terminators and automated sequencers. Sequences were phylogenetically analyzed by neighbor joining. The six new Ethiopian sequences were all subtype C, consistent with previous partial and full genome analysis. Together with two other Ethiopian sequences, the new sequences formed a geographic cluster when the complete genome was analyzed. However, subgenomic trees showed only a weak geographic cluster, or none, with respect to Ethiopian strains. Although immunological responses must be considered, from a phylogenetic perspective, there is no compelling support for use of Ethiopian subtype C sequences, compared to other subtype C, as vaccine prototype strains.
HIV-1基因多样性对候选疫苗的影响尚不确定。在评估HIV-1疫苗时,尽量减少基因多样性的一种方法是使疫苗序列与疫苗队列中的主要亚型相匹配。超过两百万埃塞俄比亚人感染了HIV-1,据认为主要亚型是C亚型。了解埃塞俄比亚序列之间以及C亚型内部的系统发育关系有助于确定候选疫苗应包含哪些序列。为此,使用近乎全基因组测序来表征从埃塞俄比亚移民的志愿者的HIV-1。从外周血单核细胞(PMBC)中提取的DNA使用长末端重复序列中的引物进行扩增,以生成近乎全长的基因组。扩增子用染料终止剂和自动测序仪直接测序。通过邻接法对序列进行系统发育分析。这六个新的埃塞俄比亚序列均为C亚型,与先前的部分和全基因组分析一致。当分析完整基因组时,新序列与另外两个埃塞俄比亚序列一起形成了一个地理集群。然而,亚基因组树显示,对于埃塞俄比亚菌株而言,仅存在一个较弱的地理集群,或者不存在地理集群。尽管必须考虑免疫反应,但从系统发育的角度来看,与其他C亚型相比,没有令人信服的证据支持使用埃塞俄比亚C亚型序列作为疫苗原型菌株。