title: Removal of either N-glycan site from the envelope receptor binding domain of Moloney and Friend but not AKV mouse ecotropic gammaretroviruses alters receptor usage.
abstract: Three N-linked glycosylation sites were removed from the envelope glycoproteins of Friend, Moloney, and AKV mouse ecotropic gammaretroviruses: gs1 and gs2, in the receptor binding domain; and gs8, in a region implicated in post-binding cell fusion. Mutants were tested for their ability to infect rodent cells expressing 4 CAT-1 receptor variants. Three mutants (Mo-gs1, Mo-gs2, and Fr-gs1) infect NIH 3T3 and rat XC cells, but are severely restricted in Mus dunni cells and Lec8, a Chinese hamster cell line susceptible to ecotropic virus. This restriction is reproduced in ferret cells expressing M. dunni dCAT-1, but not in cells expressing NIH 3T3 mCAT-1. Virus binding assays, pseudotype assays, and the use of glycosylation inhibitors further suggest that restriction is primarily due to receptor polymorphism and, in M. dunni cells, to glycosylation of cellular proteins. Virus envelope glycan size or type does not affect infectivity. Thus, host range variation due to N-glycan deletion is receptor variant-specific, cell-specific, virus type-specific, and glycan site-specific.
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0460, USA.
authors: Ryan C
authors: RC
authors: Knoper
authors: John
authors: J
authors: Ferrarone
authors: Yuhe
authors: Y
authors: Yan
authors: Bernard A P
authors: BA
authors: Lafont
authors: Christine A
authors: CA
authors: Kozak
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005289:Ferrets; D005622:Friend murine leukemia virus / Q000502:physiology; D006031:Glycosylation; D009052:Leukemia Virus, Murine / Q000502:physiology*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D051381:Rats; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D014759:Viral Envelope Proteins