Identifier

etd-04032007-191751

Degree

Master of Science (MS)

Department

Veterinary Medical Sciences - Pathobiological Sciences

Document Type

Thesis

Abstract

Viral infections of the central nervous system (CNS) in infants are rare; however, they are associated with high morbidity and mortality rates. These virus infections often induce strong innate immune responses in the brain including: the production of cytokines and chemokines, the activation of astrocytes and microglia and the recruitment of macrophages. Innate immune responses are often initiated by toll-like receptors (TLR). Several studies have demonstrated that toll-like receptor 7 (TLR7) can be stimulated by single-stranded RNA from multiple viruses. In the current study, we examined the mechanism by which TLR7 contributes to neuroinflammation in the neonatal brain using a mouse model of polytropic retrovirus infection. We found that TLR7 deficiency had no effect on neurologic disease, viral replication, or induction of interferon beta mRNA. However, TLR7 deficiency significantly altered neuroinflammatory responses including proinflammatory cytokine production, astrocyte activation, and microglial/macrophage activation. To our knowledge, this is the first demonstration of the necessity of TLR7 for innate immune responses to retrovirus infection in vivo. Additionally, this indicates that the immune response to retrovirus in the CNS may not be essential for disease pathogenesis in neonates.

Date

2007

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Karin Peterson

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