Pivotal Role of Receptor-Interacting Protein Kinase 1 and Mixed Lineage Kinase Domain-Like in Neuronal Cell Death Induced by the Human Neuroinvasive Coronavirus OC43

• DOI: 10.1128/jvi.01513-16
• Publication Date: 2016-10-20T03:24:21Z
• Authors: Mathieu Meessen-P...; Alain Le Coupanec; Marc Desforges; Pierre J. Talbot
• Keywords: Coronavirus

Human coronaviruses (HCoV) are respiratory pathogens with neuroinvasive, neurotropic, and neurovirulent properties, highlighting the importance of studying potential implication these viruses in neurological diseases. The OC43 strain (HCoV-OC43) was reported to induce neuronal cell death, which may participate neuropathogenesis. Here, we show that HCoV-OC43 harboring two point mutations spike glycoprotein (rOC/Us183-241) more than wild-type (rOC/ATCC) mice induced death murine human cells. To evaluate role regulated (RCD) HCoV-OC43-mediated neural pathogenesis, determined if knockdown Bax, a key regulator apoptosis, or RIP1, necroptosis, altered percentage following infection. We found Bax-dependent apoptosis did not play significant RCD infection, as inhibition Bax expression mediated by RNA interference confer cellular protection against process. On other hand, demonstrated RIP1 MLKL were involved chemical significantly increased survival after Taken together, results indicate contribute necroptotic infection limit viral replication. However, this could lead loss mouse CNS accentuate neuroinflammation process, reflecting severity neuropathogenesis.Because they naturally neuroinvasive suspected development Given is induces explored response characterizing activation RCD. Our revealed classical associated protein does HCoV-OC43-induced MLKL, proteins usually necroptosis (an back-up system when adequately induced), both pivotal As disrupts membranes allows release damage-associated molecular patterns (DAMP) possibly production proinflammatory cytokines, it represent mechanism contributes excessive neurodegeneration eventually disorders coronavirus