Project description:Human astrovirus infection is known to disrupt intestinal barrier function by increasing barrier permeabilty. However, the exact cellular mechanism(s) involved is unknown. We used microarrays to detail the global gene expression changes occuring during astrovirus infection and identify necessary cellular pathways for astrovirus pathogenesis.
Project description:The cellular response to astrovirus infection is not well defined. We used single cell RNA sequencing (scRNA-seq) to determine cellular response to astrovirus early or late in infection.
Project description:Infections of the central nervous system (CNS) in humans are on the rise due to changing environmental conditions and increase in vulnerable populations comprised of immunocompromised subjects with primary (genetic) or secondary (acquired) immunodeficiency. Many viruses take the opportunity to invade the CNS by capitalizing on impaired immunity of the host. Here we investigate neuropathogenesis of a rare CNS infection in immunocompromised patients caused by the astrovirus and show that it shares many features with another opportunistic infection of the CNS associated with human immunodeficiency virus. We show that astrovirus infects CNS neurons with a major impact on the brainstem. This leads to disrupted synaptic integrity loss of afferent innervation related to infected neurons and global impairment of both excitatory and inhibitory neurotransmission. In the settings of impaired peripheral adaptive immunity host responses to astrovirus infection are dominated by the microglia-macrophage-phagocytosis axis which may be a common compensatory defense mechanism employed by the CNS against opportunistic infections.
