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 Lukacher

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Murine polyomavirus
Polyomavirus
Interferon Type I
interferons
varespladib methyl
T-lymphocytes
Viruses
T-Lymphocytes
viruses
infection
tropisms
mice
Polyomavirus Infections
Tropism
Infection
interferon-beta
mutants
receptors
capsid
dendritic cells

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

Cite this

@article{2b78ed3917a04ef29401d565ff250db3,
title = "Type I interferons regulate the magnitude and functionality of mouse polyomavirus-specific CD8 T cells in a virus strain- dependent manner",
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.",
author = "Qingsong Qin and Shwetank and Frost, {Elizabeth L.} and Saumya Maru and Aron Lukacher",
year = "2016",
month = "5",
day = "1",
doi = "10.1128/JVI.00199-16",
language = "English (US)",
volume = "90",
pages = "5187--5199",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "10",

}

Type I interferons regulate the magnitude and functionality of mouse polyomavirus-specific CD8 T cells in a virus strain- dependent manner. / Qin, Qingsong; Shwetank; Frost, Elizabeth L.; Maru, Saumya; Lukacher, Aron.

In: Journal of virology, Vol. 90, No. 10, 01.05.2016, p. 5187-5199.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Type I interferons regulate the magnitude and functionality of mouse polyomavirus-specific CD8 T cells in a virus strain- dependent manner

AU - Qin, Qingsong

AU - Shwetank,

AU - Frost, Elizabeth L.

AU - Maru, Saumya

AU - Lukacher, Aron

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84977134209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977134209&partnerID=8YFLogxK

U2 - 10.1128/JVI.00199-16

DO - 10.1128/JVI.00199-16

M3 - Article

VL - 90

SP - 5187

EP - 5199

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 10

ER -