Srinivas R V, Birkedal B, Owens R J, Anantharamaiah G M, Segrest J P, Compans R W
Department of Microbiology, University of Alabama, Birmingham 35294.
Virology. 1990 May;176(1):48-57. doi: 10.1016/0042-6822(90)90229-k.
Apolipoprotein A-I (apo A-I), the major protein component of serum high density lipoproteins, was found to inhibit herpes simplex virus (HSV)-induced cell fusion at physiological (approximately 1 microM) concentrations. An 18 amino acid-long synthetic amphipathic alpha-helical peptide analog of apo A-I (18A) was also found to inhibit HSV-induced cell fusion at similar concentration (approximately 2 microM). Dimers of 18A connected via a proline (37pA) or an alanine (37aA) residue also inhibited virus-induced cell fusion at similar concentration, suggesting that the presence of a proline turn does not influence the antiviral activity of the amphipathic peptides. However, a peptide analog 18R, in which the distribution of charged residues was reversed, inhibited virus-induced cell fusion only at a higher (approximately 125 microM) concentration, suggesting that the anti-viral activity of the amphipathic peptide is strongly influenced by the nature of the charge distribution at the polar-nonpolar interface. Consistent with their ability to inhibit virus-induced cell fusion, the peptides inhibited the spread of HSV infection as demonstrated by a 10-fold reduction in the virus yield, when virus-infected cells were maintained in the presence of amphipathic peptides. The amphipathic peptides also inhibited penetration of virus into cells, but did not exert any effect on virus adsorption. A nearly complete inhibition of virus penetration was observed when the virus, or both virus and cells, was pretreated with the peptide, suggesting that the peptides may have a direct effect on the virus. The results indicate that amphipathic helices may be useful in designing novel antiviral agents that inhibit penetration and spread of enveloped viruses.
载脂蛋白A-I（apo A-I）是血清高密度脂蛋白的主要蛋白质成分，发现在生理浓度（约1微摩尔）下可抑制单纯疱疹病毒（HSV）诱导的细胞融合。还发现apo A-I的一种由18个氨基酸组成的合成两亲性α-螺旋肽类似物（18A）在相似浓度（约2微摩尔）下也能抑制HSV诱导的细胞融合。通过脯氨酸（37pA）或丙氨酸（37aA）残基连接的18A二聚体在相似浓度下也能抑制病毒诱导的细胞融合，这表明脯氨酸转角的存在不影响两亲性肽的抗病毒活性。然而，一种带电残基分布相反的肽类似物18R仅在较高浓度（约125微摩尔）下能抑制病毒诱导的细胞融合，这表明两亲性肽的抗病毒活性受极性-非极性界面电荷分布性质的强烈影响。与它们抑制病毒诱导细胞融合的能力一致，当病毒感染的细胞在两亲性肽存在下培养时，这些肽抑制了HSV感染的传播，病毒产量降低了10倍。两亲性肽还抑制病毒进入细胞，但对病毒吸附没有任何影响。当病毒或病毒与细胞都用该肽预处理时，观察到病毒穿透几乎完全被抑制，这表明这些肽可能对病毒有直接作用。结果表明，两亲性螺旋可能有助于设计新型抗病毒药物，抑制包膜病毒的穿透和传播。
