Infectious entry of murine retroviruses into mouse cells: evidence of a postadsorption step inhibited by acidic pH

Abstract

Early events in the infectious entry of mouse retroviruses are examined, using as a framework the observation that infection of a mouse tail skin cell line by the ecotropic virus Friend murine leukemia virus was inhibited at mildly acidic pH (pH 6). This inhibition operated on a postadsorption step, since binding of virus was unaffected at this pH. The rate of penetration of preadsorbed virus, which displayed 1st-order kinetics, was markedly affected by changes in the pH of the medium. The half-time for disappearance of infectious cell surface virus at 37.degree. C was .apprx. 10 min at pH 7.6. At pH 6.0, however, > 98% of the absorbed infectivity remained at the cell surface after 45 min. This cell surface virus, though not infecting the cell at pH 6.0, retained its capacity to enter and infect the cell when the pH of the medium was raised. Acidic pH had little effect on the rate of fluid uptake by the cells, as measured by internalization of [3H]sucrose, indicating that global inhibition of endocytosis had not occurred. In contrast, cell fusion induced by Friend murine leukemia virus was optimal at pH 7.6 but markedly inhibited at a pH of < 6.4. This inhibitory effect of acidic pH on membrane fusion is unique among the enveloped viruses which were studied and would preclude entry of Friend murine leukemia virus from within acidified endocytic vesicles. Entry of other members of the ecotropic, mink cell focus-forming, and xenotropic host range groups displayed similar pH sensitivity. However, 1 xenotropic virus was relatively resistant to the effect of acidic pH, suggesting that differences might exist in the requirements for entry of different retroviruses.