Foot-and-mouth disease virus 5’-terminal S fragment is required for replication and modulation of the innate immune response in host cells

Anna Kloc, Fayna Diaz-San Segundo, Elizabeth A. Schafer, Devendra K. Rai, Mary Kenney, Teresa de los Santos, Elizabeth Rieder

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The S fragment of the FMDV 5’ UTR is predicted to fold into a long stem-loop structure and it has been implicated in virus-host protein interactions. In this study, we report the minimal S fragment sequence required for virus viability and show a direct correlation between the extent of the S fragment deletion mutations and attenuated phenotypes. Furthermore, we provide novel insight into the role of the S fragment in modulating the host innate immune response. Importantly, in an FMDV mouse model system, all animals survive the inoculation with the live A24 FMDV-S4 mutant, containing a 164 nucleotide deletion in the upper S fragment loop, at a dose 1000 higher than the one causing lethality by parental A24 FMDV, indicating that the A24 FMDV-S4 virus is highly attenuated in vivo. Additionally, mice exposed to high doses of live A24 FMDV-S4 virus are fully protected when challenged with parental A24 FMDV virus.

Original languageEnglish (US)
Pages (from-to)132-143
Number of pages12
JournalVirology
Volume512
DOIs
StatePublished - Dec 2017

Bibliographical note

Funding Information:
This research was supported in part by the Plum Island Animal Disease Research Participation Program administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Department of Agriculture (appointment of Dr. Anna Kloc). We would like to thank Betty Bishop and James Zhu for providing the EBK cell line, and Dr. Michael Puckette for technical assistance with the Veritas Microplate Luminometer. Appendix A

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 project no. 8064-32000-061-00D , Agricultural Research Service (ARS), U.S. Department of Agriculture (Dr. Elizabeth Rieder).

Publisher Copyright:
© 2017

Keywords

  • FMDV S fragment
  • Foot-and-mouth disease virus
  • Innate immunity against virus
  • Picornavirus

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