Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis at the Blood-Brain Barrier for Central Nervous System Entry
Abstract
VEEV, WEEV, and eastern equine encephalitis virus (EEEV) are emerging infectious diseases in the Americas, and they have caused several major outbreaks in the human and horse population during the past few decades. Shortly after infection, these viruses can infect the CNS, resulting in severe long-term neurological deficits or death. Neuroinvasion has been associated with virus entry into the CNS directly from the bloodstream; however, the underlying molecular mechanisms have remained largely unknown. Here, we demonstrate that following peripheral infection alphavirus augments vesicular formation/trafficking at the BBB and utilizes Cav-MT to cross an intact BBB, a process regulated by activators of Rho GTPases within brain endothelium. In vivo examination of early viral entry in Cav-1-deficient mice revealed significantly lower viral burdens in the brain than in similarly infected wild-type animals. These studies identify a potentially targetable pathway to limit neuroinvasion by alphaviruses.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 25, 2020
- Source ID
- 10.1128/mbio.02731-19
Entities
People
- Chengqun Sun
- Hamid Salimi
- Jianghui Hou
- Matthew D. Cain
- Robyn A. Roth
- Robyn Klein
- Wandy L. Beatty
- William B Klimstra
- Xiaoping Jiang
Organizations
- Defense Threat Reduction Agency
- National Institute of Allergy and Infectious Diseases
- University of Pittsburgh
- Washington University School of Medicine
- Washington University in St. Louis