Evolutionary pressure of a receptor competitor selects different subgroup A avian leukosis virus escape variants with altered receptor interactions

Deborah C. Melder, V. Shane Pankratz, Mark J Federspiel

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A complex interaction between the retroviral envelope glycoproteins and a specific cell surface protein initiates viral entry into cells. The avian leukosis-sarcoma virus (ALV) group of retroviruses provides a useful experimental system for studying the retroviral entry process and the evolution of receptor usage. In this study, we demonstrate that evolutionary pressure on subgroup A ALV [ALV(A)] entry exerted by the presence of a competitive inhibitor, a soluble form of the ALV(A) Tva receptor linked to a mouse immunoglobulin G tag (quail sTva-mIgG), can select different populations of escape variants. This escape population contained three abundant ALV(A) variant viruses, all with mutations in the surface glycoprotein hypervariable regions: a previously identified variant containing the Y142N mutation in the hr1 region; a new variant with two mutations, W141G in hr1 and K261E in vr3; and another new variant with two mutations, W145R in hr1 and K261E. The W141G K261E and W145R K261E viruses escape primarily by lowering their binding affinities for the quail Tva receptor competitive inhibitor while retaining wild-type levels of binding affinity for the chicken Tva receptor. A secondary phenotype of the new variants was an alteration in receptor interference patterns from that of wild-type ALV(A), indicating that the mutant glycoproteins are possibly interacting with other cellular proteins. One result of these altered interactions was that the variants caused a transient period of cytotoxicity. We could also directly demonstrate that the W141G K261E variant glycoproteins bound significant levels of a soluble form of the TvbS3 ALV receptor in a binding assay. Alterations in the normally extreme specificity of the ALV(A) glycoproteins for Tva may represent an evolutionary first step toward expanding viral receptor usage in response to inefficient viral entry.

Original languageEnglish (US)
Pages (from-to)10504-10514
Number of pages11
JournalJournal of Virology
Volume77
Issue number19
DOIs
StatePublished - Oct 2003

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Alpharetrovirus
Avian Leukosis Virus
Avian leukosis virus
avian leukosis
sarcoma
Pressure
viruses
receptors
glycoproteins
Glycoproteins
mutation
Mutation
Quail
quails
Retroviridae
Rous sarcoma virus
Viruses
Virus Receptors
Virus Internalization
selection pressure

ASJC Scopus subject areas

  • Immunology

Cite this

Evolutionary pressure of a receptor competitor selects different subgroup A avian leukosis virus escape variants with altered receptor interactions. / Melder, Deborah C.; Pankratz, V. Shane; Federspiel, Mark J.

In: Journal of Virology, Vol. 77, No. 19, 10.2003, p. 10504-10514.

Research output: Contribution to journalArticle

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