title: Escape from R-peptide deletion in a γ-retrovirus.
abstract: The R peptide in the cytoplasmic tail (C-tail) of γ-retroviral envelope proteins (Env) prevents membrane fusion before budding. To analyse its role in the formation of replication competent, infectious particles, we developed chimeric murine leukaemia viruses (MLV) with unmodified or R-peptide deleted Env proteins of the gibbon ape leukaemia virus (GaLV). While titres of these viruses were unaffected, R-peptide deficiency led to strongly impaired spreading. Most remarkably, we isolated an escape mutant which had restored an open reading frame for a C-terminal extension of the truncated C-tail. A reconstituted virus encoding this escape C-tail replicated in cell culture. In contrast to R-peptide deficient Env, particle incorporation of the escape Env was effective due to an enhanced protein expression and restored intracellular co-localisation with Gag proteins. Our data demonstrate that the R peptide not only regulates membrane fusion but also mediates efficient Env protein particle incorporation in γ-retrovirus infected cells.
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
authors.forename: Irene C
authors.initials: IC
authors.lastname: Schneider
authors.forename: Manon
authors.initials: M
authors.lastname: Eckhardt
authors.forename: Julia
authors.initials: J
authors.lastname: Brynza
authors.forename: Mary K
authors.initials: MK
authors.lastname: Collins
authors.forename: Klaus
authors.initials: K
authors.lastname: Cichutek
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Buchholz
mesh_terms: D000818:Animals; D002460:Cell Line; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006801:Humans; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D016865:Reassortant Viruses / Q000235:genetics; D012190:Retroviridae / Q000145:classification* / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D009842:Oligopeptides; C080708:R peptide; D014764:Viral Proteins