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: Heather H Cheng, Maria M Anderson, F Claire Hankenson, Lily Johnston, Chitra V Kotwaliwale, Julie Overbaugh
• Journal: Journal of virology (J Virol) Vol. 80 Issue 4 Pg. 1619-28 (Feb 2006) ISSN: 0022-538X [Print] United States
• PMID: 16439518 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Virus
• Retroviridae Proteins, Oncogenic
• Viral Envelope Proteins
• feline leukemia virus receptor
• glycoprotein gp70, Feline leukemia virus

Topics

• Amino Acid Substitution
• Animals
• Binding Sites (genetics)
• Cell Line
• Humans
• Leukemia Virus, Feline (genetics, physiology)
• Mice
• Mutagenesis, Site-Directed
• Mutation
• Receptors, Virus (physiology)
• Retroviridae Proteins, Oncogenic (genetics, physiology)
• Viral Envelope Proteins (genetics, physiology)