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dc.contributor.advisorEvelyn A. Kurt-Jones, Ph.D.
dc.contributor.authorMacKay, Christopher R.
dc.date2022-08-11T08:08:46.000
dc.date.accessioned2022-08-23T16:07:36Z
dc.date.available2022-08-23T16:07:36Z
dc.date.issued2017-05-30
dc.date.submitted2017-06-13
dc.identifier.doi10.13028/M2602R
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32281
dc.description.abstractAfter initially being infected with a virus, before an adaptive immune response can be mounted, the innate immune system of a cell recognizes and responds to certain patterns present in pathogenic molecules. I studied the role of two genes—PIR1 and CD200R1—on the innate immune responses in two different mouse models of viral infection, infection with the picornavirus EMCV (encephalomyocarditis virus) and infection with HSV-1 (herpes simplex virus) in a mouse model of herpes simplex encephalitis, respectively. PIR1 is a putative RNA phosphatase that has been shown to play an important role in antiviral small RNA processing in C. elegans. It has also been shown to interact with the RIG-I-like receptor LGP2 in preliminary mammalian experiments. I sought to characterize the effect PIR1 has on the innate immune response to the virus EMCV in mice. By developing a PIR1-null mouse, I have found that the role of PIR1 in the progression of EMCV in mice is limited. However, in vitro studies show that PIR1 might play an important role in regulating foreign RNA recognition during the earliest time points post-infection. CD200R1 is an anti-inflammatory signaling molecule that is expressed on myeloidderived cells, and whose ligand is highly expressed within the central nervous system. I investigated the role of this receptor in an intracranial model of herpes simplex encephalitis. CD200R1KO mice show improved survival following direct intracranial infection with HSV. I found this increased survival can be attributed to decreased levels of viral replication in CD200R1KO compared to wild-type mice. Further investigation has shown that CD200R1 affects the signaling and upregulation of the pattern-recognition receptor TLR-2 (toll-like receptor 2), and thus CD200R1 may impact HSV-1 replication by affecting TLR2 signaling.
dc.language.isoen_US
dc.rightsLicensed under a Creative Commons license
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectinnate immunity
dc.subjectinnate immune response
dc.subjectPIR1
dc.subjectCD200R1
dc.subjectEMCV
dc.subjectencephalomyocarditis virus
dc.subjectHSV-1
dc.subjectherpes simplex virus
dc.subjectImmunity
dc.subjectImmunology of Infectious Disease
dc.subjectPathogenic Microbiology
dc.subjectVirology
dc.titleInvestigating the Role of PIR1 and CD200R1 in the Innate Immune Response to Viral Pathogens
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1905&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/901
dc.legacy.embargo2019-06-13T00:00:00-07:00
dc.identifier.contextkey10288960
refterms.dateFOA2022-08-27T04:55:11Z
html.description.abstract<p>After initially being infected with a virus, before an adaptive immune response can be mounted, the innate immune system of a cell recognizes and responds to certain patterns present in pathogenic molecules. I studied the role of two genes—PIR1 and CD200R1—on the innate immune responses in two different mouse models of viral infection, infection with the picornavirus EMCV (encephalomyocarditis virus) and infection with HSV-1 (herpes simplex virus) in a mouse model of herpes simplex encephalitis, respectively.</p> <p>PIR1 is a putative RNA phosphatase that has been shown to play an important role in antiviral small RNA processing in C. elegans. It has also been shown to interact with the RIG-I-like receptor LGP2 in preliminary mammalian experiments. I sought to characterize the effect PIR1 has on the innate immune response to the virus EMCV in mice. By developing a PIR1-null mouse, I have found that the role of PIR1 in the progression of EMCV in mice is limited. However, in vitro studies show that PIR1 might play an important role in regulating foreign RNA recognition during the earliest time points post-infection.</p> <p>CD200R1 is an anti-inflammatory signaling molecule that is expressed on myeloidderived cells, and whose ligand is highly expressed within the central nervous system. I investigated the role of this receptor in an intracranial model of herpes simplex encephalitis. CD200R1KO mice show improved survival following direct intracranial infection with HSV. I found this increased survival can be attributed to decreased levels of viral replication in CD200R1KO compared to wild-type mice. Further investigation has shown that CD200R1 affects the signaling and upregulation of the pattern-recognition receptor TLR-2 (toll-like receptor 2), and thus CD200R1 may impact HSV-1 replication by affecting TLR2 signaling.</p>
dc.identifier.submissionpathgsbs_diss/901
dc.contributor.departmentInfectious Diseases and Immunology
dc.description.thesisprogramMD/PhD
dc.identifier.orcid0000-0002-7734-363X


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