Mechanisms of Viral Pathogenesis in the Central Nervous System

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

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. This year, we have continued our studies on vertical transmission (VTn) of Zika virus (ZIKV). In previous years, we developed and characterized a mouse model that showed clear vertical transmission of ZIKV from dam to fetus (Winkler et al. Immunology 2018; Winkler et al. J. Immunol. 2017, Winkler et al. Sci. Rep. 2017). In 2020, we published a manuscript showing that placental myeloid cells from the mother were protective against Zika virus vertical transmission (Winkler et al. J. Immunology 2020). We also collaborated on a study with Dan Chertow's group in Bethesda showing that in utero exposure to Zika virus was not protective against reinfection by Zika virus at 1 year postpartum (Vannella et al. Sci. Transl. Med. 2020). In 2020-2021, we also published on our continuing studies of how virus infection affects the blood brain barrier (BBB) and brain capillary endothelial cells (BCECs). We previously demonstrated that La Crosse Virus (LACV) gains access to the CNS by causing vascular leakage in BCECs, primarily in the olfactory bulb/tract region of the brain (Winkler et al. Acta Neuropath 2015). We have collaborated with Dr. Iain Frasers laboratory in Bethesda to examine differences in BCEC between different regions of the brain as well as studying how age impacts virus-induced damage to these cells. In our current research, we showed that BCECs isolated from young mice were more sensitive to virus-infection as well as virus-induced damage compared to BCECs isolated from adult mice (Basu et al. J. Neuroinflammation. 2021). Ongoing studies have identified several genes that are differentially expressed between adult and weanling BCECs that impact virus infection both in vitro as well as in vivo. These studies should be published within the next year. We also collaborated with Dr. Hasenkrugs lab at RML in a study to examine how the macrophage dont eat me signal protein, CD47, influences immune responses to LACV infection (Tal et al. mBio 2020). In addition, we published a book chapter on Orthobunyaviruses (Evans et al. Orthobunyaviruses in Encyclopedia of Viruses, 4th edition 2020).