Role of Jumonji C-domain containing protein 6 (JMJD6) in infectivity of foot-and-mouth disease virus

Paul Lawrence, Devendra Rai, Joseph S. Conderino, Sabena Uddowla, Elizabeth Rieder

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Foot-and-mouth disease virus (FMDV) utilizes four integrins (αvβ1, αvβ3, αvβ6, and αvβ8) as its primary cell receptor. During cell culture propagation, FMDV frequently adapts to use heparan sulfate (HS), and rarely utilizes an unidentified third receptor. Capsid mutations acquired by a soluble integrin resistant FMDV cause (i) adaptation to CHO-677 cells (ii) increased affinity to membrane-bound Jumonji C-domain containing protein 6 (JMJD6) (iii) induced JMJD6 re-localization from the cell surface and cytoplasm to the nucleus. Interestingly, pre-treatment of cells with N- and C-terminal JMJD6 antibodies or by simultaneous incubation of mutant virus with soluble JMJD6 (but not by treatment with HS or αvβ6) impaired virus infectivity in cultured cells. JMJD6 and mutant virus co-purified by reciprocal co-immunoprecipitation. Molecular docking predictions suggested JMJD6 C-terminus interacts with mutated VP1 capsid protein. We conclude when specific VP1 mutations are displayed, JMJD6 contributes to FMDV infectivity and may be a previously unidentified FMDV receptor.

Original languageEnglish (US)
Pages (from-to)38-52
Number of pages15
JournalVirology
Volume492
DOIs
StatePublished - May 1 2016

Bibliographical note

Funding Information:
Funding for the research detailed in this manuscript was provided through Congressionally allocated dollars for the Agricultural Research Service of the United States Department of Agriculture.

Keywords

  • FMDV alternate receptor
  • Foot-and-mouth disease virus (FMDV)
  • Jumonji C-domain containing protein 6 (JMJD6)

Fingerprint Dive into the research topics of 'Role of Jumonji C-domain containing protein 6 (JMJD6) in infectivity of foot-and-mouth disease virus'. Together they form a unique fingerprint.

Cite this