Jubier-Maurin V, Saragosti S, Perret J L, Mpoudi E, Esu-Williams E, Mulanga C, Liegeois F, Ekwalanga M, Delaporte E, Peeters M
Laboratoire Retrovirus, ORSTOM, Montpellier, France.
AIDS Res Hum Retroviruses. 1999 Jan 1;15(1):23-32. doi: 10.1089/088922299311673.
Most efforts to characterize sequence variation of HIV isolates has been directed toward the structural envelope gene. Few studies have evaluated the sequence variability of auxiliary genes such as nef. In this study 41 new HIV-1 strains, representing the majority of the described envelope subtypes of HIV-1 (A to H), were genetically characterized in the nef region. Phylogenetic analysis showed that 34 strains could be classified in the same subtype in nef and env, and 7 (19%) of the 41 new viruses were recombinants. For two of the seven strains, recombination occurred upstream of the nef gene, whereas for five of the seven strains recombination occurred within the nef gene with a crossover close to the 5' end of the LTR (long terminal repeat). The low intersubtype distance between subtype B and D in the nef gene confirms previous observations in the pol, env, and gag genes, which suggest a common ancestor for these subtypes. The majority of all the previously described functional domains in the nef gene were relatively conserved among the different subtypes, with only minor differences being observed. The myristoylation signal among the different subtypes, with only minor differences being observed. The myristoylation signal was less conserved for subtype C, with one or more amino acid changes being observed at positions 3, 4, and 5. The highly conserved acidic region (positions 62 to 65), critical for the enhancement of viral synthesis with an increased virus growth rate, was less conserved among the subtype G strains from our study. At least three epitopic regions of the nef gene have been defined and each can be recognized by CTLs under a variety of HLA restrictions; all were also relatively well conserved between the different genetic subtypes. Despite the relatively important genetic variation in nef sequences obtained among the different genetic subtypes, functional domains and CTL epitopes were relatively well conserved. In vitro and/or in vivo studies are necessary to study the relevance of the observed differences.
大多数对HIV分离株序列变异特征的研究都集中在结构包膜基因上。很少有研究评估辅助基因如nef的序列变异性。在本研究中，对41株新的HIV-1毒株（代表了HIV-1描述的大多数包膜亚型，即A至H）的nef区域进行了基因特征分析。系统发育分析表明，34株毒株在nef和env中可归为同一亚型，41株新病毒中有7株（19%）是重组体。在这7株毒株中，有2株的重组发生在nef基因上游，而另外5株的重组发生在nef基因内部，交叉点靠近长末端重复序列（LTR）的5'端。nef基因中B亚型和D亚型之间的低亚型间距离证实了之前在pol、env和gag基因中的观察结果，这表明这些亚型有共同的祖先。在不同亚型中，nef基因中所有先前描述的功能结构域大多相对保守，仅观察到微小差异。不同亚型间的肉豆蔻酰化信号仅观察到微小差异。C亚型的肉豆蔻酰化信号保守性较差，在第3、4和5位观察到一个或多个氨基酸变化。在我们研究的G亚型毒株中，对病毒合成增强和病毒生长速率增加至关重要的高度保守的酸性区域（第62至65位）保守性较差。nef基因至少已定义了三个表位区域，并且在多种HLA限制下每个区域都能被细胞毒性T淋巴细胞（CTL）识别；在不同的基因亚型之间它们也相对保守。尽管在不同基因亚型中获得的nef序列存在相对重要的遗传变异，但功能结构域和CTL表位相对保守。需要进行体外和/或体内研究来探讨所观察到差异的相关性。
