| Popis: |
Ts 1, a temperature-sensitive mutant of Moloney murine leukemia virus-TB (MoMuLV-TB), causes a progressive hindlimb paralytic disease in susceptible strains of mice. Previously, it has been shown that a single amino acid substitution, Val-25→Ile in gPr80 env , is responsible for the temperature sensitivity, inefficient transport, and processing of gPr80 env at the restrictive temperature and the neurovirulence of ts 1. Since the neurovirulence of ts 1 is associated with inefficient transport and processing of gPr80 env and since in other systems involving viral envelope proteins it has been shown that correct folding and oligomerization of envelope monomers are required for efficient transport, we have investigated the ability of gPr80 env derived from either wild-type MoMuLV-TB or ts 1 to associate into oligomeric complexes. In these experiments, we establish that at both the restrictive and the nonrestrictive temperatures gPr80 env molecules derived from MoMuLV-TB associate to form oligomeric complexes and these oligomers are most likely trimers. gPr80 env molecules derived from tsl also oligomerize at both temperatures; however, at the restrictive temperature, most of the molecules within the trimeric complexes remain as gPr80 env and are not processed to gp70 and Prpl 5E. These results indicate that lack of oligomerization of gPr80 env is not responsible for the transport defect of ts 1. Therefore, by interacting specifically with critical sites within target cells, oligomers of mutant gPr80 env rather than “tangles” of monomeric viral envelope proteins may be involved in the neurodegenerative disorder produced by ts1 . |
