This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Subproject #1: Persistent norovirus infection of lymphoid tissue impairs protective immunity Stephanie M. Karst Human noroviruses in the Caliciviridae family are the major cause of nonbacterial gastroenteritis outbreaks worldwide and are emerging pathogens of public health interest. The major goal of this project is to design rationale vaccination strategies to prevent norovirus infection. Human norovirus infection does not induce lasting immunity, potentially a very important observation in terms of rationale vaccine design. We have now recapitulated this atypical pattern of immunity in the mouse model ?primary MNV-1 infection of mice fails to elicit memory immune responses that protect from mucosal infection or disease. Accumulating evidence by our group and others demonstrates that noroviruses cause persistent infection of lymphoid tissues. We initially hypothesized that persistent viral replication in lymphoid compartments impairs the generation of protective immune responses. However, we have now determined that a second murine norovirus strain, MNV-3, which persistently infects mice for a longer duration than does MNV-1 actually elicits protective immunity. Thus, there does not appear to be a direct correlation between the length of persistent MNV infection and the magnitude of protection afforded by a primary challenge. Interestingly, there is a correlation between protective immunity induction and cell tropism. We therefore hypothesize that MNV infection of mucosal antigen presenting cells impairs the development of protective memory immunity.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018724-07
Application #
7959551
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2009-05-01
Project End
2010-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
7
Fiscal Year
2009
Total Cost
$211,337
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
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
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
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

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