Yamaguchi-Kabata Yumi, Yamashita Masahiro, Ohkura Sadayuki, Hayami Masanori, Miura Tomoyuki
Integrated Database Group, Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, 2-41-6 Aomi, Koto-ku, Tokyo 135-0064, Japan.
J Mol Evol. 2004 Mar;58(3):333-40. doi: 10.1007/s00239-003-2555-x.
To clarify the relationship between the amino acid variations of the gp120 of human immunodeficiency virus type 1 (HIV-1) and the chemokine receptors that are used as the second receptor for HIV, we evaluated amino acid site variation of gp120 between the X4 strains (use CXCR4) and the R5 strains (use CCR5) from 21 sequences of subtype B. Our analysis showed that residues 306 and 322 in the V3 loop and residue 440 in the C4 region were associated with usage of the second receptor. The polymorphism at residue 440 is clearly associated with the usage of the second receptor: The amino acid at position 440 was a basic amino acid in the R5 strains, and a nonbasic and smaller amino acid in the X4 strains, while the V3 loop of the X4 strains was more basic than that of the R5 strains. This suggests that residue 440 in the C4 region, which is close to the V3 loop in the three-dimensional structure, is critical in determining which second receptor is used. Analysis of codon frequency suggests that, in almost all cases, the difference at residue 440 between basic amino acids in the R5 strains and nonbasic amino acids in the X4 strains could be due to a single nucleotide change. These findings predict that the evolutionary changes in amino acid residue 440 may be correlated with evolutionary changes in the V3 loop. One possibility is that a change in electric charge at residue 440 compensates for a change in electric charge in the V3 loop. The amino acid polymorphism at position 440 can be useful to predict the cell tropism of a strain of HIV-1 subtype B.
为了阐明人类免疫缺陷病毒1型（HIV-1）的gp120氨基酸变异与用作HIV第二受体的趋化因子受体之间的关系，我们评估了来自21个B亚型序列的X4毒株（使用CXCR4）和R5毒株（使用CCR5）之间gp120的氨基酸位点变异。我们的分析表明，V3环中的306和322位残基以及C4区域中的440位残基与第二受体的使用相关。440位残基处的多态性与第二受体的使用明显相关：440位氨基酸在R5毒株中为碱性氨基酸，在X4毒株中为非碱性且较小的氨基酸，而X4毒株的V3环比R5毒株的更具碱性。这表明在三维结构中靠近V3环的C4区域中的440位残基对于确定使用哪种第二受体至关重要。密码子频率分析表明，在几乎所有情况下，R5毒株中的碱性氨基酸与X4毒株中的非碱性氨基酸在440位残基处的差异可能是由于单个核苷酸变化所致。这些发现预测，440位氨基酸残基的进化变化可能与V3环的进化变化相关。一种可能性是440位残基处电荷的变化补偿了V3环中电荷的变化。440位氨基酸多态性可用于预测HIV-1 B亚型毒株的细胞嗜性。
