title: MAVS protein is attenuated by rotavirus nonstructural protein 1.
abstract: Rotavirus is the single, most important agent of infantile gastroenteritis in many animal species, including humans. In developing countries, rotavirus infection attributes approximately 500,000 deaths annually. Like other viruses it establishes an intimate and complex interaction with the host cell to counteract the antiviral responses elicited by the cell. Among various pattern recognition receptors (PAMPs) of the host, the cytosolic RNA helicases interact with viral RNA to activate the Mitochondrial Antiviral Signaling protein (MAVS), which regulates cellular interferon response. With an aim to identify the role of different PAMPs in rotavirus infected cell, MAVS was found to degrade in a time dependent and strain independent manner. Rotavirus non-structural protein 1 (NSP1) which is a known IFN antagonist, interacted with MAVS and degraded it in a strain independent manner, resulting in a complete loss of RNA sensing machinery in the infected cell. To best of our knowledge, this is the first report on NSP1 functionality where a signaling protein is targeted unanimously in all strains. In addition NSP1 inhibited the formation of detergent resistant MAVS aggregates, thereby averting the antiviral signaling cascade. The present study highlights the multifunctional role of rotavirus NSP1 and reinforces the fact that the virus orchestrates the cellular antiviral response to its own benefit by various back up strategies.
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India.
authors.forename: Satabdi
authors.initials: S
authors.lastname: Nandi
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India.
authors.forename: Shampa
authors.initials: S
authors.lastname: Chanda
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India.
authors.forename: Parikshit
authors.initials: P
authors.lastname: Bagchi
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India.
authors.forename: Mukti Kant
authors.initials: MK
authors.lastname: Nayak
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhowmick
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Chawla-Sarkar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D019073:HT29 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D059748:Proteolysis; D012401:Rotavirus / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015853:Cysteine Proteinase Inhibitors; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D007976:Leupeptins; C505371:MAVS protein, human; D017361:Viral Nonstructural Proteins; C104282:nsp1 protein, Rotavirus; D016899:Interferon-beta; D008156:Luciferases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde