Okada T, Gurney M E
Department of Cell, Molecular, and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
AIDS Res Hum Retroviruses. 1995 May;11(5):571-5. doi: 10.1089/aid.1995.11.571.
The third variable domain (V3 domain) of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 contains a substantial number of positively charged amino acid residues. We previously demonstrated that mutation of basic amino acid residues at position 303, 306, 309, 313, and 325 in the V3 domain of HIV-1 strain NL4-3 resulted in a dramatic elimination of both virus infectivity and syncytium-inducing ability. Mutations of arginine at position 302 to serine (R302S) or lysine at position 320 to glutamine (K320Q) had variable effects on infectivity for a panel of T cell lines tested. These mutations are located on opposite sides of the Gly-Pro-Gly-Arg-Ala sequence in the center of the V3 domain. The R302S and K320Q mutations allowed us to determine if these basic residues are important for virus neutralization by polyanionic compounds. Dextran sulfate and heparin inhibited the cytopathogenicities of both mutants for MT-4 cells, although their 50% antiviral effective doses were slightly higher than those required to achieve complete protection against wild-type HIV-1NL4-3 replication. This result emphasizes that the basic amino acids of Arg302 and Lys320 are not essential for the inhibitory effect of dextran sulfate and heparin on HIV-1 infection.
人类免疫缺陷病毒1型（HIV-1）包膜糖蛋白gp120的第三个可变区（V3区）含有大量带正电荷的氨基酸残基。我们先前证明，HIV-1毒株NL4-3的V3区中第303、306、309、313和325位碱性氨基酸残基的突变导致病毒感染性和诱导合胞体能力显著消除。第302位精氨酸突变为丝氨酸（R302S）或第320位赖氨酸突变为谷氨酰胺（K320Q），对一组测试的T细胞系的感染性有不同影响。这些突变位于V3区中心的甘氨酸-脯氨酸-甘氨酸-精氨酸-丙氨酸序列的两侧。R302S和K320Q突变使我们能够确定这些碱性残基对于多阴离子化合物中和病毒是否重要。硫酸葡聚糖和肝素抑制了两种突变体对MT-4细胞的细胞致病性，尽管它们的50%抗病毒有效剂量略高于实现完全保护免受野生型HIV-1 NL4-3复制所需的剂量。这一结果强调，精氨酸302和赖氨酸320的碱性氨基酸对于硫酸葡聚糖和肝素对HIV-1感染的抑制作用并非必不可少。
