Spatial Uncoupling of Protein Synthesis from Viral Factories during Rabies Virus Infection
Replication and transcription of Mononegavirales (MNV) occur in cytoplasmic viral factories. In rabies virus (RABV) infected cells, these membrane-less, liquid-liquid phase-separated organelles are called Negri bodies (NBs). Their accumulation of viral mRNAs suggests that, in addition to supporting viral RNA synthesis, they may also serve as sites of viral protein translation. Using…
Rabies virus (RABV) replication and transcription take place within cytoplasmic viral factories known as Negri bodies (NBs). These membrane-less, liquid-liquid phase-separated organelles accumulate viral mRNAs, suggesting they might also facilitate viral protein translation. By utilizing immunofluorescence and confocal microscopy, researchers observed that ribosomal subunit proteins and translation initiation factors, including the ribosomal protein RPL40, are excluded from NBs.
This exclusion occurs despite NBs playing a role in RABV's unconventional translation initiation mechanism.
To further understand protein synthesis dynamics during RABV infection, the team conducted pulse-labeling experiments using the methionine analogue homopropargylglycine (HPG). The results showed a rapid accumulation of newly synthesized proteins within NBs, independent of microtubule and actin cytoskeletons. Additionally, RABV infection induced the formation of stress granules (SGs), where some ribosomal proteins and translation initiation factors congregated.
Interestingly, cells with SGs exhibited a significant inhibition of protein synthesis. Overall, these findings reveal that translation occurs outside NBs in RABV infected cells, followed by the targeted delivery of nascent viral proteins to these specialized compartments.
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