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 to tumors induced by MPyV from epithelial to mesenchymal cell origin. Here, we asked if this tropism difference affected the MPyV-specific CD8 T cell response, which controls MPyV infection and tumorigenesis. Infection by the laboratory MPyV strain RA (VP1-91G) or 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 A2(VP1-91E) infection. Mutant A2(91G)-infected mice showed a higher frequency of memory precursor (CD127(hi)KLRG1(lo)) CD8 T cells and a higher recall response than A2-infected mice. Using 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. 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 interferon (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 infection. 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.
PMID: 26984726 [PubMed - as supplied by publisher]