Comprehensive Mutational Analysis of the Moloney Murine Leukemia Virus Envelope Protein
AUTOR(ES)
Rothenberg, S. Michael
FONTE
American Society for Microbiology
RESUMO
The envelope (Env) protein of Moloney murine leukemia virus is the primary mediator of viral entry. We constructed a large pool of insertion mutations in the env gene and analyzed the fitness of each mutant in completing two critical steps in the virus life cycle: (i) the expression and delivery of the Env protein to the cell surface during virion assembly and (ii) the infectivity of virions displaying the mutant proteins. The majority of the mutants were poorly expressed at the producer cell surface, suggesting folding defects due to the presence of the inserted residues. The mutants with residual infectivity had insertions either in the amino-terminal signal sequence region, two disulfide-bonded loops in the receptor binding domain, discrete regions of the carboxy-terminal region of the surface subunit (SU), or the cytoplasmic tail. Insertions that allowed the mutants to reach the cell surface but not to mediate detectable infection were located within the amino-terminal sequence of the mature Env, within the SU carboxy-terminal region, near putative receptor binding residues, and throughout the fusion peptide. Independent analysis of select mutants in this group allowed more precise identification of the defect in Env function. Mapping of mutant phenotypes to a structural model of the receptor-binding domain provides insights into the protein's functional organization. The high-resolution functional map reported here will be valuable for the engineering of the Env protein for a variety of uses, including gene therapy.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=114771Documentos Relacionados
- Mutational analysis of the envelope gene of Moloney murine leukemia virus.
- Mutational analysis of the N-linked glycosylation sites of the SU envelope protein of Moloney murine leukemia virus.
- Mutational analysis of the carboxyl terminus of the Moloney murine leukemia virus integration protein.
- Functional analysis of the cytoplasmic tail of Moloney murine leukemia virus envelope protein.
- Mutational Analysis of the Fusion Peptide of Moloney Murine Leukemia Virus Transmembrane Protein p15E