Mechanisms of Viral Pathogenesis in the Central Nervous System

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

The innate immune response to virus infection has a strong influence on virus infection in the brain and the clinical outcome of disease. Our studies have focused on animal models of virus-mediated neuropathogenesis to determine the host response proteins that regulate disease induction for virus replication and viral pathogenesis. In 2017 and 2018, we developed a model for vertical transmission (VTn) of Zika virus to fetuses, with the subsequent development of microcephaly in the newborn mouse pup (Winkler et al. Immunology 2018, unpublished observations). This model was based on our previously published work on Zika virus (Winkler et al. J. Immunol. 2017, Winkler et al. Sci. Rep. 2017). This model is currently being used to analyze how virus is transmitted from the dam to the fetus, the role of innate immune cells in this viral transmission, how the virus is transmitted to the brain in the fetus and the role of the innate immune response to brain damage in the fetus. Our studies on La Crosse Virus (LACV), a primary cause of pediatric arboviral encephalitis in the USA, focused on the role of inflammatory cells recruited to the brain by virus infection. Using a mouse model, we found that the main immune cell recruited to the brain was the inflammatory monocyte. Importantly, in studying the role of the role of inflammatory monocytes in the disease process, we discovered a novel mechanism by which virus infection can induce monocyte recruitment from the bone marrow into the blood. These results were published in the Journal of Immunology (Winkler et al. J. Immunol. 2018).