Volume 23, No 8, Aug 2013

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 23 Issue 8, August 2013: 1025-1042

ORIGINAL ARTICLES

Viral degradasome hijacks mitochondria to suppress innate immunity

Ramansu Goswami^1,*, Tanmay Majumdar^1,*, Jayeeta Dhar¹, Saurabh Chattopadhyay², Sudip K Bandyopadhyay², Valentina Verbovetskaya¹, Ganes C Sen² and Sailen Barik¹

¹Center for Gene Regulation in Health and Disease, and Department of Biological, Geological and Environmental Sciences, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA
²Department of Molecular Genetics, Lerner Research Institute of the Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA Correspondence: Sailen Barik, Tel: +1-216-523-7326; Fax: +1-216-687-6972(s.barik@csuohio.edu)

The balance between the innate immunity of the host and the ability of a pathogen to evade it strongly influences pathogenesis and virulence. The two nonstructural (NS) proteins, NS1 and NS2, of respiratory syncytial virus (RSV) are critically required for RSV virulence. Together, they strongly suppress the type I interferon (IFN)-mediated innate immunity of the host cells by degrading or inhibiting multiple cellular factors required for either IFN induction or response pathways, including RIG-I, IRF3, IRF7, TBK1 and STAT2. Here, we provide evidence for the existence of a large and heterogeneous degradative complex assembled by the NS proteins, which we named “NS-degradasome” (NSD). The NSD is roughly ~300-750 kD in size, and its degradative activity was enhanced by the addition of purified mitochondria in vitro. Inside the cell, the majority of the NS proteins and the substrates of the NSD translocated to the mitochondria upon RSV infection. Genetic and pharmacological evidence shows that optimal suppression of innate immunity requires mitochondrial MAVS and mitochondrial motility. Together, we propose a novel paradigm in which the mitochondria, known to be important for the innate immune activation of the host, are also important for viral suppression of the innate immunity.

10.1038/cr.2013.98

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