McClure M O, Marsh M, Weiss R A
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
EMBO J. 1988 Feb;7(2):513-8. doi: 10.1002/j.1460-2075.1988.tb02839.x.
The effect of weak bases (NH4Cl and amantadine) and carboxylic ionophores (monensin) on the infection of CD4 (T4) positive human cell lines by HIV-1 is examined. These reagents, which raise the pH of acidic intracellular organelles, fail to inhibit HIV-1 entry and the events leading to viral protein synthesis at concentrations inhibitory for low pH-dependent fusogenic enveloped viruses. The infectivity of VSV (HIV-1) pseudotypes is unaffected by weak bases at concentrations causing 95% plaque reduction of VSV in its own envelope. HIV-1 dependent cell--cell fusion (syncytium formation) occurs in medium maintained at pH 7.4-7.6, and virions are not irreversibly inactivated by incubation in acid medium. Our results show that HIV-1 entry and membrane fusion do not require exposure to low pH. The production of infectious HIV-1 particles, however, is inhibited in cells treated with NH4Cl.
研究了弱碱(氯化铵和金刚烷胺)和羧酸离子载体(莫能菌素)对HIV-1感染CD4(T4)阳性人细胞系的影响。这些能提高酸性细胞内细胞器pH值的试剂,在对低pH依赖性融合包膜病毒具有抑制作用的浓度下,未能抑制HIV-1的进入以及导致病毒蛋白合成的事件。VSV(HIV-1)假型的感染性不受弱碱的影响,而相同浓度的弱碱可使VSV自身包膜的空斑减少95%。HIV-1依赖的细胞间融合(合胞体形成)发生在pH值维持在7.4 - 7.6的培养基中,并且病毒粒子在酸性培养基中孵育不会被不可逆地灭活。我们的结果表明,HIV-1的进入和膜融合不需要暴露于低pH环境。然而,用氯化铵处理的细胞中感染性HIV-1颗粒的产生受到抑制。