Year: 2015
Type: article
Abstract: Coxsackievirus B3 (CVB), an enterovirus, is a small, ssRNA virus with a genome of approximately 7 kB. There are 2 million symptomatic CVB infections annually in the United States, ranging from mild febrile illnesses to myocarditis, meningoencephalitis, or pancreatitis. CVB is a fecal-oral pathogen and must overcome diverse cellular barriers to cause disease, including the polarized epithelium lining the gastrointestinal tract. Viral infection of a host cell results in a variety of cellular responses that serve to control the viral infection. Once such response is the activation of intracellular innate immune signaling; this results in the production of type I interferon, which signals in an auto- and paracrine fashion to alter the transcriptional profile of a cell to inhibit viral replication. A second response to viral infection is the induction of cell death pathways; as viruses utilize host cell machinery for replication, early cell death of a host cell can result in an abortive infection. Here, I examine the ways in which CVB interfaces with these host cell pathways that affect viral replication. A primary mechanism utilized by CVB for altering host cell pathways is the production of the virally-encoded cysteine protease 3Cpro. 3Cpro is required to process the viral polypeptide but is also known to target cellular protein targets for proteolysis. Here, I identify two cellular proteins targeted for proteolysis by 3Cpro, Unc93b and RIP3, that are involved in the intracellular innate immune signaling and cell death pathways, respectively. I then characterize the roles of these proteins and their cleavage during CVB infection. In summary, I explore the ways in which CVB manipulates its host cell through proteolysis of host cell proteins by the virally-encoded protease 3Cpro and find that the balance between virus and host is finely tuned through the activity of this protease.
Author: Katharine G. Harris
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1011169295