A unique variant of lymphocytic choriomeningitis virus that induces pheromone binding protein MUP: Critical role for CTL

Brian C Ware; Brian M Sullivan; Stephanie LaVergne; Brett S Marro; Toru Egashira; Kevin P Campbell; John Elder; Michael B. A Oldstone

doi:10.1073/pnas.1907070116

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A unique variant of lymphocytic choriomeningitis virus that induces pheromone binding protein MUP: Critical role for CTL

Journal article

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A unique variant of lymphocytic choriomeningitis virus that induces pheromone binding protein MUP: Critical role for CTL

Brian C Ware, Brian M Sullivan, Stephanie LaVergne, Brett S Marro, Toru Egashira, Kevin P Campbell, John Elder and Michael B. A Oldstone

Proceedings of the National Academy of Sciences - PNAS, Vol.116(36), pp.18001-18008

09/03/2019

DOI: 10.1073/pnas.1907070116

PMCID: PMC6731760

PMID: 31427525

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Abstract

Lymphocytic choriomeningitis virus (LCMV) WE variant 2.2 (v2.2) generated a high level of the major mouse urinary protein: MUP. Mice infected with LCMV WE v54, which differed from v2.2 by a single amino acid in the viral glycoprotein, failed to generate MUP above baseline levels found in uninfected controls. Variant 54 bound at 2.5 logs higher affinity to the LCMV receptor α-dystroglycan (α-DG) than v2.2 and entered α-DG–expressing but not α-DG–null cells. Variant 2.2 infected both α-DG–null or –expressing cells. Variant 54 infected more dendritic cells, generated a negligible CD8 T cell response, and caused a persistent infection, while v2.2 generated cytotoxic T lymphocytes (CTLs) and cleared virus within 10 days. By 20 days postinfection and through the 80-day observation period, significantly higher amounts of MUP were found in v2.2-infected mice. Production of MUP was dependent on virus-specific CTL as deletion of such cells aborted MUP production. Furthermore, MUP production was not elevated in v2.2 persistently infected mice unless virus was cleared following transfer of virus-specific CTL.

Biological Sciences

lymphocytic choriomeningitis virus (LCMV)

cytotoxic T lymphocytes (CTL)

pheromones

MUP

Details

Title: Subtitle: A unique variant of lymphocytic choriomeningitis virus that induces pheromone binding protein MUP: Critical role for CTL
Creators: Brian C Ware - Viral-Immunobiology Laboratory, Department of Immunology and Microbiology
Brian M Sullivan - Viral-Immunobiology Laboratory, Department of Immunology and Microbiology
Stephanie LaVergne - Viral-Immunobiology Laboratory, Department of Immunology and Microbiology
Brett S Marro - Viral-Immunobiology Laboratory, Department of Immunology and Microbiology
Toru Egashira - Department of Molecular Physiology, Roy J. and Lucille A. Carver College of Medicine
Kevin P Campbell - Department of Molecular Physiology, Roy J. and Lucille A. Carver College of Medicine
John Elder - Department of Immunology and Microbiology
Michael B. A Oldstone - Viral-Immunobiology Laboratory, Department of Immunology and Microbiology
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.116(36), pp.18001-18008
DOI: 10.1073/pnas.1907070116
PMID: 31427525
PMCID: PMC6731760
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Grant note: AI099699 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32 AI007036 / HHS | National Institutes of Health (NIH) AI009484 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U54 NS053672 / HHS | National Institutes of Health (NIH)
Language: English
Date published: 09/03/2019
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984068375302771

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