A Val-25-to-Ile substitution in the envelope precursor polyprotein, gPr80 super(env), is responsible for the temperature sensitivity, inefficient processing of gPr80 super(env), and neurovirulence of ts1, a mutant of Moloney murine leukemia virus TB

ts1 is a neurovirulent spontaneous temperature-sensitive mutant of Moloney murine leukemia virus TB which causes hindlimb paralysis in mice. Previously, it had been shown that the temperature-sensitive defect resided in the env gene. At the restrictive temperature, the envelope precursor polyprotein...

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Bibliographic Details
Published inJournal of virology Vol. 64; no. 2; pp. 467 - 475
Main Authors Szurek, P F, Yuen, PH, Ball, J K, Wong, PKY
Format Journal Article
LanguageEnglish
Published 01.01.1990
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Summary:ts1 is a neurovirulent spontaneous temperature-sensitive mutant of Moloney murine leukemia virus TB which causes hindlimb paralysis in mice. Previously, it had been shown that the temperature-sensitive defect resided in the env gene. At the restrictive temperature, the envelope precursor polyprotein, gPr80 super(env), is inefficiently processed intracellularly into two cleavage products, gp70 and Prp15E. This inefficient processing of gPr80 super(env) is correlated with neurovirulence. In this study, it was shown that a single amino acid substitution, Val-25 arrow right Ile in gPr80 super(env), is responsible for the temperature sensitivity, inefficient processing of gPr80 super(env) at the restrictive temperature, and neurovirulence of ts1. At the restrictive temperature, a steady-state level of nonprocessed, endoglycosidase H-sensitive gPr80 super(env) remained in the endoplasmic reticulum of cells infected by ts1, but no endoglycosidase H-resistant gPr80 super(env) and only trace amounts of gp70 were detected in the infected cells. Since the host cell-encoded processing protease resides in the cis cisternae of the Golgi apparatus, inefficient processing of gPr80 super(env) at the restrictive temperature is most likely due to inefficient transport of gPr80 super(env) from the endoplasmic reticulum to the cis cisternae of the Golgi apparatus.
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ISSN:0022-538X