Mutations in Both the Surface and Transmembrane Envelope Glycoproteins of the RAV-2 Subgroup B Avian Sarcoma and Leukosis Virus Are Required to Escape the Antiviral Effect of a Secreted Form of the TvbS3 Receptor †

Xueqian Yin, Deborah C. Melder, William S. Payne, Jerry B. Dodgson, Mark J Federspiel

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The subgroup A through E avian sarcoma and leukosis viruses ASLV(A) through ASLV(E) are a group of highly related alpharetroviruses that have evolved to use very different host protein families as receptors. We have exploited genetic selection strategies to force the replication-competent ASLVs to naturally evolve and acquire mutations to escape the pressure on virus entry and yield a functional replicating virus. In this study, evolutionary pressure was exerted on ASLV(B) virus entry and replication using a secreted for of its Tvb receptor. As expected, mutations in the ASLV(B) surface glycoprotein hypervariable regions were selected that knocked out the ability for the mutant glycoprotein to bind the sTvbS3-IgG inhibitor. However, the subgroup B Rous associated virus 2 (RAV-2) also required additional mutations in the C-terminal end of the SU glycoprotein and multiple regions of TM highlighting the importance of the entire viral envelope glycoprotein trimer structure to mediate the entry process efficiently. These mutations altered the normal two-step ASLV membrane fusion process to enable infection.

Original languageEnglish (US)
JournalViruses
Volume11
Issue number6
DOIs
StatePublished - May 31 2019

Fingerprint

Avian Sarcoma Viruses
Avian Leukosis Virus
Cercopithecine Herpesvirus 1
Antiviral Agents
Glycoproteins
Alpharetrovirus
Virus Internalization
Mutation
Pressure
Membrane Fusion
Genetic Selection
Membrane Glycoproteins
Virus Replication
Immunoglobulin G
Viruses
Infection
Proteins

Keywords

  • avian sarcoma and leukosis viruses
  • envelope glycoprotein evolution
  • receptor usage

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

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abstract = "The subgroup A through E avian sarcoma and leukosis viruses ASLV(A) through ASLV(E) are a group of highly related alpharetroviruses that have evolved to use very different host protein families as receptors. We have exploited genetic selection strategies to force the replication-competent ASLVs to naturally evolve and acquire mutations to escape the pressure on virus entry and yield a functional replicating virus. In this study, evolutionary pressure was exerted on ASLV(B) virus entry and replication using a secreted for of its Tvb receptor. As expected, mutations in the ASLV(B) surface glycoprotein hypervariable regions were selected that knocked out the ability for the mutant glycoprotein to bind the sTvbS3-IgG inhibitor. However, the subgroup B Rous associated virus 2 (RAV-2) also required additional mutations in the C-terminal end of the SU glycoprotein and multiple regions of TM highlighting the importance of the entire viral envelope glycoprotein trimer structure to mediate the entry process efficiently. These mutations altered the normal two-step ASLV membrane fusion process to enable infection.",
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AU - Payne, William S.

AU - Dodgson, Jerry B.

AU - Federspiel, Mark J

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