This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Subproject #5: The Role of Platelets in Cytomegalovirus-Induced Inflammatory Disease Karen Y. Stokes Inflammation is a key component of cardiovascular disease, and it is recognized that platelets actively participate in the inflammatory responses to different cardiovascular risk factors. It is recognized that platelets actively participate in the inflammatory responses to different cardiovascular risk factors. Cytomegalovirus (CMV) is a cardiovascular risk factor that employs inflammatory mechanisms in order to disseminate and survive, this being a potential link between CMV and cardiovascular disease. In isolated cells, CMV can also induce platelet activation and adhesion however the role of platelets in CMV-induced inflammation remains unclear. We have a murine CMV (mCMV) model in which we can monitor responses of small vessels to infection, and have observed that mCMV infection promotes vessel dysfunction in arterioles, and with the introduction of hypercholesterolemia also induces an inflammatory and thrombogenic phenotype in venules. We hypothesize that platelets mediate CMV-induced microvascular inflammatory responses through interactions with (and activation of) other cells types, and that hypercholesterolemia exaggerates these responses. We will employ mutant mice, and antibodies to deplete platelets or block platelet surface receptors/counter-receptors, to test our hypothesis in our mCMV model. Our initial findings show that, regardless of diet, microvascular responses during CMV infection are dependent on P-selection, an adhesion molecule upregulated on platelets during CMV infection. Short-term depletion of platelets partially protects against CMV-induced arteriolar dysfunction and the accompanying venular inflammation during CMV infection in high cholesterol subjects. This proposal should provide novel insights into the thrombogenic potential of CMV and how it synergizes with other risk factors to exacerbate platelet activation, and therefore may reveal a target for early therapeutic intervention against cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018724-09
Application #
8359695
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
9
Fiscal Year
2011
Total Cost
$209,859
Indirect Cost
Name
Louisiana State University Hsc Shreveport
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
095439774
City
Shreveport
State
LA
Country
United States
Zip Code
71103
Kim, Jung Heon; Collins-McMillen, Donna; Buehler, Jason C et al. (2017) Human Cytomegalovirus Requires Epidermal Growth Factor Receptor Signaling To Enter and Initiate the Early Steps in the Establishment of Latency in CD34+ Human Progenitor Cells. J Virol 91:
Martinez, Nicholas E; Sato, Fumitaka; Kawai, Eiichiro et al. (2015) Th17-biased ROR?t transgenic mice become susceptible to a viral model for multiple sclerosis. Brain Behav Immun 43:86-97
Kawai, Eiichiro; Sato, Fumitaka; Omura, Seiichi et al. (2015) Organ-specific protective role of NKT cells in virus-induced inflammatory demyelination and myocarditis depends on mouse strain. J Neuroimmunol 278:174-84
Stevenson, Emily V; Collins-McMillen, Donna; Kim, Jung Heon et al. (2014) HCMV reprogramming of infected monocyte survival and differentiation: a Goldilocks phenomenon. Viruses 6:782-807
Coleman, Carrie B; McGraw, Jennifer E; Feldman, Emily R et al. (2014) A gammaherpesvirus Bcl-2 ortholog blocks B cell receptor-mediated apoptosis and promotes the survival of developing B cells in vivo. PLoS Pathog 10:e1003916
Fernando, Viromi; Omura, Seiichi; Sato, Fumitaka et al. (2014) Regulation of an autoimmune model for multiple sclerosis in Th2-biased GATA3 transgenic mice. Int J Mol Sci 15:1700-18
Martinez, Nicholas E; Karlsson, Fridrik; Sato, Fumitaka et al. (2014) Protective and detrimental roles for regulatory T cells in a viral model for multiple sclerosis. Brain Pathol 24:436-51
Sato, Fumitaka; Omura, Seiichi; Kawai, Eiichiro et al. (2014) Distinct kinetics of viral replication, T cell infiltration, and fibrosis in three phases of myocarditis following Theiler's virus infection. Cell Immunol 292:85-93
DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Hilbig, Lydia et al. (2014) The nuclear retention signal of HPV16 L2 protein is essential for incoming viral genome to transverse the trans-Golgi network. Virology 458-459:93-105
Sato, Fumitaka; Martinez, Nicholas E; Shahid, Maira et al. (2013) Resveratrol exacerbates both autoimmune and viral models of multiple sclerosis. Am J Pathol 183:1390-1396

Showing the most recent 10 out of 92 publications