Oligomerization and transport of the envelope protein of Moloney murine leukemia virus-TB and of ts1, a neurovirulent temperature-sensitive mutant of MoMuLV-TB.
Ts1, 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 gPr80env, is responsible for the temperature sensitivity, inefficient transport, and processing of gPr80env at the restrictive temperature and the neurovirulence of ts1. Since the neurovirulence of ts1 is associated with inefficient transport and processing of gPr80env 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 gPr80env derived from either wild-type MoMuLV-TB or ts1 to associate into oligomeric complexes. In these experiments, we establish that at both the restrictive and the nonrestrictive temperatures gPr80env molecules derived from MoMuLV-TB associate to form oligomeric complexes and these oligomers are most likely trimers. gPr80env molecules derived from ts1 also oligomerize at both temperatures; however, at the restrictive temperature, most of the molecules within the trimeric complexes remain as gPr80env and are not processed to gp70 and Prp15E. These results indicate that lack of oligomerization of gPr80env is not responsible for the transport defect of ts1. Therefore, by interacting specifically with critical sites within target cells, oligomers of mutant gPr80env rather than "tangles" of monomeric viral envelope proteins may be involved in the neurodegenerative disorder produced by ts1.
Kamps
C A
CA
University of Texas M. D. Anderson Cancer Center, Smithville 78957.
Lin
Y C
YC
Wong
P K
PK
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D015686:Gene Products, env / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008979:Moloney murine leukemia virus / Q000378:metabolism* / Q000472:pathogenicity; D009154:Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013696:Temperature; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
D015686:Gene Products, env; D046911:Macromolecular Substances; D014759:Viral Envelope Proteins