Uncovering differences between virus-specific primary and secondary effector CD4 T cells

Mice infected with the neuroattenuated rJ2.2 strain of the murine coronavirus, mouse hepatitis virus (MHV), develop acute encephalitis and acute and chronic demyelinating diseases. The pathogenesis of rJ2.2 serves as an animal model for the human disease multiple sclerosis (MS) because animals develop clinical and histopathological changes similar to those seen in patients. The immunopathological consequence of demyelination unveils the delicate balance between pro-inflammatory factors required for viral clearance and anti-inflammatory factors necessary for limiting tissue damage. Virus specific CD4 T cells are critical for viral clearance and play a role in the development of demyelination. My project seeks to understand the differences between virus-specific primary and secondary effector CD4 T cells.

Athmer J, Fehr AR, Grunewald ME, Qu W, Wheeler DL, Graepel KW, Channappanavar R, Sekine A, Aldabeeb DS, Gale M Jr, Denison MR, Perlman S. Selective Packaging in Murine Coronavirus Promotes Virulence by Limiting Type I Interferon Responses. MBio. 2018 May 1;9(3). pii: e00272-18. doi: 10.1128/mBio.00272-18. PubMed PMID: 29717007; PubMed Central PMCID: PMC5930304.

Wheeler DL, Sariol A, Meyerholz DK, Perlman S. Microglia are required for protection against lethal coronavirus encephalitis in mice. J Clin Invest. 2018 Mar 1;128(3):931-943. doi: 10.1172/JCI97229. Epub 2018 Jan 29. PubMed PMID:29376888; PubMed Central PMCID: PMC5824854.

Wheeler DL, Athmer J, Meyerholz DK, Perlman S. Murine Olfactory Bulb Interneurons Survive Infection with a Neurotropic Coronavirus. J Virol. 2017 Aug 23. pii: JVI.01099-17. doi: 10.1128/JVI.01099-17. [Epub ahead of print] PubMed PMID: 28835503.

Vijay R, Fehr AR, Janowski AM, Athmer J, Wheeler DL, Grunewald M, Sompallae R, Kurup SP, Meyerholz DK, Sutterwala FS, Narumiya S, Perlman S. Virus-induced inflammasome activation is suppressed by prostaglandin D(2)/DP1 signaling. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5444-E5453. doi:10.1073/pnas.1704099114. Epub 2017 Jun 19. PubMed PMID: 28630327; PubMed Central PMCID: PMC5502630.

Mielech AM, Deng X, Chen Y, Kindler E, Wheeler DL, Mesecar AD, Thiel V, Perlman S, Baker SC. Murine coronavirus ubiquitin-like domain is important for papain-like protease stability and viral pathogenesis. J Virol. 2015 May;89(9):4907-17. doi: 10.1128/JVI.00338-15. Epub 2015 Feb 18. PubMed PMID:25694594; PubMed Central PMCID: PMC4403493.

Book Chapter:

Wheeler DL, and Perlman S. Neurotropic coronavirus infections. Reiss C.S. Neurotropic viral infections. Springer.