Khrustalev Vladislav Victorovich
Department of General Chemistry, Belarussian State Medical University, Minsk 220000, Belarus.
In Silico Biol. 2009;9(4):255-69.
Guanine is the most mutable nucleotide in HIV genes because of frequently occurring G to A transitions, which are caused by cytosine deamination in viral DNA minus strands catalyzed by APOBEC enzymes. Distribution of guanine between three codon positions should influence the probability for G to A mutation to be nonsynonymous (to occur in first or second codon position). We discovered that nucleotide sequences of env genes coding for third variable regions (V3 loops) of gp120 from HIV1 and HIV2 have different kinds of guanine usage biases. In the HIV1 reference strain and 100 additionally analyzed HIV1 strains the guanine usage bias in V3 loop coding regions (2G>1G>>3G) should lead to elevated nonsynonymous G to A transitions occurrence rates. In the HIV2 reference strain and 100 other HIV2 strains guanine usage bias in V3 loop coding regions (3G>2G>1G) should protect V3 loops from hypermutability. According to the HIV1 and HIV2 V3 alignment, insertion of the sequence enriched with 2G (21 codons in length) occurred during the evolution of HIV1 predecessor, while insertion of the different sequence enriched with 3G (19 codons in length) occurred during the evolution of HIV2 predecessor. The higher is the level of 3G in the V3 coding region, the lower should be the immune escaping mutation occurrence rates. This hypothesis was tested in this study by comparing the guanine usage in V3 loop coding regions from HIV1 fast and slow progressors. All calculations have been performed by our algorithms "VVK In length", "VVK Dinucleotides" and "VVK Consensus" (www.barkovsky.hotmail.ru).
由于频繁发生的G到A的转换，鸟嘌呤是HIV基因中最易发生突变的核苷酸，这种转换是由载脂蛋白B mRNA编辑酶催化的病毒DNA负链中的胞嘧啶脱氨作用引起的。鸟嘌呤在三个密码子位置之间的分布应会影响G到A突变成为非同义突变（发生在第一或第二密码子位置）的概率。我们发现，编码HIV-1和HIV-2的gp120第三可变区（V3环）的env基因的核苷酸序列存在不同类型的鸟嘌呤使用偏好。在HIV-1参考毒株和另外100株分析的HIV-1毒株中，V3环编码区的鸟嘌呤使用偏好（2G>1G>>3G）应会导致非同义G到A转换的发生率升高。在HIV-2参考毒株和其他100株HIV-2毒株中，V3环编码区的鸟嘌呤使用偏好（3G>2G>1G）应会保护V3环免于高度可变。根据HIV-1和HIV-2的V3比对，富含2G的序列（长度为21个密码子）的插入发生在HIV-1前身的进化过程中，而富含3G的不同序列（长度为19个密码子）的插入发生在HIV-2前身的进化过程中。V3编码区中3G的水平越高，免疫逃逸突变的发生率应该越低。本研究通过比较HIV-1快速进展者和缓慢进展者的V3环编码区中的鸟嘌呤使用情况来检验这一假设。所有计算均由我们的算法“VVK In length”、“VVK Dinucleotides”和“VVK Consensus”（www.barkovsky.hotmail.ru）完成。
