Rabies Virus Infection Induces the Formation of Stress Granules Closely Connected to the Viral Factories

• DOI: 10.1371/journal.ppat.1005942
• Publication Date: 2016-10-17T17:29:33Z
• Authors: Jovan Nikolic; Ahmet Civas; Zoé Lama; Cécile Lagaudrièr...; Danielle Blondel
• Keywords: Stress granule; Viral structural protein; Viral protein; Antiviral protein; Viral Shedding

Stress granules (SGs) are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range environmental cellular stresses viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During infection, SG formation results the modulation innate antiviral immune responses, several viruses have ability either promote or prevent assembly. Here, we show rabies virus (RABV) induces infected cells, revealed by detection SG-marker proteins Ras GTPase-activating protein-binding 1 (G3BP1), T-cell intracellular antigen (TIA-1) poly(A)-binding (PABP) RNA formed during infection. As shown live cell imaging, RABV-induced SGs highly increase number, grow size fusion events, undergo assembly/disassembly cycles. Some localize close proximity cytoplasmic factories, known Negri bodies (NBs). Three dimensional reconstructions reveal both remain distinct even when they contact. In addition, synthesized NBs accumulate revealing material exchange between compartments. Although is not affected MEFs lacking TIA-1, TIA-1 depletion promotes translation which an replication indicating has effect. Inhibition PKR expression significantly prevents RABV-SG favors increasing translation. This correlated with drastic inhibition IFN-B gene likely mediate however sufficient fully counteract RABV