Sibil Oksayan

Monash University (Australia) · Department of Biochemistry and Molecular Biology

Multifunctionality of viral genes is critical for processes in replication and modulation of infected cells. P gene of rabies virus generates the full-length protein, P1, and the truncated isoform, P3, which gains unique phenotypes lacking in P1, including interactions with multiple cellular membrane-less organelles (MLOs, liquid-liquid phase-separ...

Rabies virus P-protein is expressed as five isoforms (P1-P5) which undergo nucleocytoplasmic trafficking important to roles in immune evasion. Although nuclear import of P3 is known to be mediated by an importin (IMP)-recognised nuclear localization sequence in the N-terminal region (N-NLS), the mechanisms underlying nuclear import of other P isofo...

Mutation of K214/R260 affects nuclear localization of P3 in neuronal and glial cells through a mechanism involving active nuclear export and impaired nuclear import. (A, B) T98G human glioblastoma and (C, D) SH-SY5Y human neuroblastoma cells transfected to express the indicated proteins were treated with or without LMB (2.8 ng/ml, 3 h) prior to ana...

IMPα2 co-precipitates with RABV P-proteins from neuronal cells, dependent on K214/R260. NA mouse neuroblastoma cells expressing the indicated GFP-fused proteins were subjected to immunoprecipitation using GFP-Trap before analysis of immunoprecipitate (IP) and whole cell lysate (WCL) by immunoblotting (IB) for IMPα2 and GFP. (TIF)

Rabies virus replicates in the cytoplasm of host cells, but rabies virus phosphoprotein (P-protein) undergoes active nucleocytoplasmic trafficking. Here we show that the largely nuclear P-protein isoform P3 can localise to nucleoli, and forms specific interactions with nucleolin. Importantly, depletion of nucleolin expression inhibits viral protein...

The evasion of host innate immunity by Rabies virus, the prototype of the genus Lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here,...

Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export...

Vesicular stomatitis virus (VSV) and Rabies Virus (RABV) are the prototypic members of the rhabdovirus family. These viruses have a particularly broad host range, and despite the availability of vaccines, RABV still causes more than 50,000 human deaths a year. Trafficking of the virion or viral particles is important at several stages of the replic...

Conventional nuclear import is independent of the cytoskeleton, but recent data have shown that the import of specific proteins can be either facilitated or inhibited by microtubules (MTs). Nuclear import of the P-protein from rabies virus involves a MT-facilitated mechanism, but here, we show that P-protein is unique in that it also undergoes MT-i...