title: Envelope determinants for dual-receptor specificity in feline leukemia virus subgroup A and T variants.
abstract: Gammaretroviruses, including the subgroups A, B, and C of feline leukemia virus (FeLV), use a multiple-membrane-spanning transport protein as a receptor. In some cases, such as FeLV-T, a nonclassical receptor that includes both a transport protein (Pit1) and a soluble cofactor (FeLIX) is required for entry. To define which regions confer specificity to classical versus nonclassical receptor pathways, we engineered mutations found in either FeLV-A/T or FeLV-T, individually and in combination, into the backbone of the transmissible form of the virus, FeLV-A. The receptor specificities of these viruses were tested by measuring infection and binding to cells expressing the FeLV-A receptor or the FeLV-T receptors. FeLV-A receptor specificity was maintained when changes at amino acid position 6, 7, or 8 of the mature envelope glycoprotein were introduced, although differences in infection efficiency were observed. When these N-terminal mutations were introduced together with a C-terminal 4-amino-acid insertion and an adjacent amino acid change, the resulting viruses acquired FeLV-T receptor specificity. Additionally, a W-->L change at amino acid position 378, although not required, enhanced infectivity for some viruses. Thus, we have found that determinants in the N and C termini of the envelope surface unit can direct entry via the nonclassical FeLV-T receptor pathway. The region that has been defined as the receptor binding domain of gammaretroviral envelope proteins determined entry via the FeLV-A receptor independently of the presence of the N- and C-terminal FeLV-T receptor determinants.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Mail Stop C3-168, Seattle, WA 98109-1024, USA.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Cheng
authors.forename: Maria M
authors.initials: MM
authors.lastname: Anderson
authors.forename: F Claire
authors.initials: FC
authors.lastname: Hankenson
authors.forename: Lily
authors.initials: L
authors.lastname: Johnston
authors.forename: Chitra V
authors.initials: CV
authors.lastname: Kotwaliwale
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D006801:Humans; D005256:Leukemia Virus, Feline / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011991:Receptors, Virus / Q000502:physiology*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D011991:Receptors, Virus; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C074548:feline leukemia virus receptor; C073723:glycoprotein gp70, Feline leukemia virus