Formation of membrane-defined compartments by tick-borne encephalitis virus contributes to the early delay in interferon signaling

Three-Dimensional Architecture of Tick-Borne Encephalitis Virus Replication Sites and Trafficking of the Replicated RNA

“…1D). These data are in agreement with our previous observations for the MS2-tagged TBEV replicon where newly synthesized viral RNA associates with viral proteins and dsRNA replication intermediates in rER-derived cytoplasmic compartments (8,19).…”

“…For this set of experiments, we used BHK21-EYFPMS2nls cells transduced with lentiviral vectors expressing the nuclear variant of the EYFP-MS2 fusion protein. Previously, in order to tag TBEV replicons, we always used a form of EYFP-tagged MS2 that localized both in the nucleus and in the cytoplasm (8,19,31). However, we noticed that the accumulation of tagged TBEV RNA in the cytoplasm corresponded to a depletion of the MS2 nuclear stain.…”

“…These sites, generally defined as replication compartments, are required to efficiently coordinate different steps of the viral life cycle and to protect replicating RNA from innate immunity surveillance (8)(9)(10). Over the last few years, several electron microscopy studies have revealed important information about the ultrastructural organization of these sophisticated intracellular membrane compartments (11,12,28).…”

“…It is generally accepted that the formation of these replication compartments (RC) provide an optimal microenvironment for viral RNA replication by limiting diffusion of viral/host proteins and viral RNA, thereby increasing the concentration of components required for RNA synthesis, and by providing a scaffold for anchoring the replication complex (7). In addition, these virus-induced membranes may also shield doublestranded RNA (dsRNA) replication intermediates from host cellintrinsic surveillance (8)(9)(10). Elegant electron tomography (ET) studies on DENV-and WNV-infected cells have recently provided the first three-dimensional (3D) view of the architecture of flavivirus RCs (11,12).…”

The Stress Granule Component TIA-1 Binds Tick-Borne Encephalitis Virus RNA and Is Recruited to Perinuclear Sites of Viral Replication To Inhibit Viral Translation

“…For instance, TBEV is able to trigger the retinoic acid-inducible gene 1 (RIG-I)-dependent antiviral pathway that leads to the activation of the type I interferons (␣/␤ interferon [IFN-␣/␤]) (9). However, other cellular mechanisms, such as the stress response pathway, are also able to limit viral infection (10).…”