Pathogenesis and micro-anatomic characterization of a cell-adapted mutant foot-and-mouth disease virus in cattle: Impact of the Jumonji C-domain containing protein 6 (JMJD6) and route of inoculation

Paul Lawrence, Juan Pacheco, Carolina Stenfeldt, Jonathan Arzt, Devendra K. Rai, Elizabeth Rieder

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

A companion study reported Jumonji-C domain containing protein 6 (JMJD6) is involved in an integrin- and HS-independent pathway of FMDV infection in CHO cells. JMJD6 localization was investigated in animal tissues from cattle infected with either wild type A24-FMDV (A24-WT) or mutant FMDV (JMJD6-FMDV) carrying E95K/S96L and RGD to KGE mutations in VP1. Additionally, pathogenesis of mutant JMJD6-FMDV was investigated in cattle through aerosol and intraepithelial lingual (IEL) inoculation. Interestingly, JMJD6-FMDV pathogenesis was equivalent to A24-WT administered by IEL route. In contrast, JMJD6-FMDV aerosol-infected cattle did not manifest signs of FMD and animals showed no detectable viremia. Immunofluorescent microscopy of post-mortem tissue revealed JMJD6-FMDV exclusively co-localized with JMJD6+ cells while A24-WT was occasionally found in JMJD6+ cells. In vitro, chemical uptake inhibitors demonstrated JMJD6-FMDV entered cells via clathrin-coated pit endocytosis. In vivo, JMJD6-FMDV exhibited preference for JMJD6+ cells, but availability of this alternative receptor likely depends on route of inoculation.

Original languageEnglish (US)
Pages (from-to)108-117
Number of pages10
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. Specifically, CRIS projects no. 1940-32000-057-00D, Agricultural Research Service (ARS), U.S. Department of Agriculture (Dr. Elizabeth Rieder).

Keywords

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

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