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Respiratory tract infections are responsible for many deaths around the globe with particularly high mortality rates for the elderly, young, or immune-compromised. Innumerable studies have identified many of the causative agents like influenzaviruses, rhinoviruses, and adenoviruses. However, ~30% of all viral respiratory infections cannot be attributed to these known viruses. Recently, strains of another family of viruses, polyomaviridae, have been identified in respiratory samples of young children on two continents. Unfortunately, very little is known about the pathogenesis of respiratory PyV infection or how the immune system responds to it. Studying a mouse model of respiratory PyV infection may provide insights that would aid in the creation of effective therapies in humans.
Polyomavirus
Literally meaning “many tumors,” polyomaviruses can induce tumor formation in certain circumstances but mainly establish persistent, asymptomatic infection.
CD8 T-cell function
CD8 T-cells are the main subset of leukocytes that handle viral infections.
Once activated, they destroy infected cells identified by expression of viral peptides (instead of self-peptides) in MHC molecules.
They also signal other immune cells by producing and secreting cytokines.
Use of Tetramer
Objectives
Track kinetics of epitope-specific CD8 T-cell expansion during intranasal (IN) infection of PyV
Determine phenotype of epitope-specific CD8 T-cells during the course of IN infection
Determine sites of viral replication and persistence for respiratory PyV infection
Hypothesis
The mucosa of the respiratory tract encounters many pathogens and must utilize efficient mechanisms to contain potential infection. Therefore, CD8 T cells should be preferentially recruited to the lungs of IN infected mice, resulting in a faster, larger, and more functional expansion of virus specific CD8 T-cells.
Kinetics of T-cell Expansion
Surface Phenotypes
Viral DNA Copies in Tissue
Intracellular production
CD8 T-cells show different phenotype in the lungs, regardless of point of inoculation.
Virus Specific T-cell expansion is significantly lower in magnitude for IN infected mice.
Tetramer + expansion follows same time course in both groups.
Hypothesis was disproved because both infections resulted in a greater expansion in the lungs.
The respiratory tract could be the primary means of PyV transmission, correlating to its high seroprevalence.
Future Directions
Use mutated strain of PyV that is more comparable to KI and WU virus in regards to cell permissivity and binding affinity.
Determine if IN infection by PyV could produce tumors
This material is based on work funded by the Howard Hughes Medical Institute under grant #52005873 and by the National Science Foundation under award #0450303.
I’d like to give a special thank you to Dr. Christopher D. Pack, Jarad Wilson, Eugene Lin and Annette Hadley for all their help with this endeavor
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