Type I interferons regulate the magnitude and functionality of mouse polyomavirus-specific CD8 T cells in a virus strain- dependent manner

Qingsong Qin, Shwetank, Elizabeth L. Frost, Saumya Maru, Aron E. Lukacher

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Mouse polyomavirus (MPyV) is a ubiquitous persistent natural mouse pathogen. A glutamic acid (E)-to-glycine (G) difference at position 91 of the VP1 capsid protein shifts the profile of tumors induced by MPyV from an epithelial to a mesenchymal cell origin. Here we asked if this tropism difference affects the MPyV-specific CD8 T cell response, which controls MPyV infection and tumorigenesis. Infection by the laboratory MPyV strain RA (VP1-91G) or a strain A2 mutant with an E-to-G substitution at VP1 residue 91 [A2(91G)] generated a markedly smaller virus-specific CD8 T cell response than that induced by A2(VP1-91E) infection. Mutant A2(91G)-infected mice showed a higher frequency of memory precursor (CD127hi KLRG1lo) CD8 T cells and a higher recall response than those of A2-infected mice. Using T cell receptor (TCR)-transgenic CD8 T cells and immunization with peptide-pulsed dendritic cells, we found that early bystander inflammation associated with A2 infection contributed to recruitment of the larger MPyV-specific CD8 T cell response. Beta interferon (IFN-β) transcripts were induced early during A2 or A2(91G) infections. IFN-β inhibited replication of A2 and A2(91G) in vitro. Using mice lacking IFN-αβ receptors (IFNAR-/-), we showed that type I IFNs played a role in controlling MPyV replication in vivo but differentially affected the magnitude and functionality of virus-specific CD8 T cells recruited by A2 and A2(91G) viral infections. These data indicate that type I IFNs are involved in protection against MPyV infection and that their effect on the antiviral CD8 T cell response depends on capsid-mediated tropism properties of the MPyV strain.

Original languageEnglish (US)
Pages (from-to)5187-5199
Number of pages13
JournalJournal of virology
Volume90
Issue number10
DOIs
StatePublished - May 1 2016

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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