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Microtubule-dependent and microtubule-independent steps in Crimean-Congo hemorrhagic fever virus replication cycle
Melinda Simon1, Cecilia Johansson, Ake Lundkvist
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. melinda.simon@smi.ki.se
Insights
Crimean-Congo hemorrhagic fever virus (CCHFV) biogenesis is impaired by microtubule disruption. Intact microtubules are crucial for CCHFV entry, replication, assembly, and egress, impacting viral RNA levels and particle release.
Area of Science:
- Virology
- Cell Biology
- Microbiology
Background:
- Viruses utilize host cell cytoskeleton for intracellular transport, assembly, and egress.
- Crimean-Congo hemorrhagic fever virus (CCHFV) interactions with host cells are not well understood.
- The cytoskeleton, particularly microtubules, plays a role in the life cycle of many viruses.
Purpose of the Study:
- To investigate the role of microtubules in the biogenesis of Crimean-Congo hemorrhagic fever virus (CCHFV).
- To determine how microtubule dynamics affect CCHFV entry, replication, assembly, and egress.
- To elucidate virus-host interactions involving the cytoskeleton during CCHFV infection.
Main Methods:
- Drug-induced suppression and disassembly of microtubule dynamics.
- Assessment of CCHFV internalization, RNA levels, and protein localization.
- Analysis of virus assembly and egress in relation to microtubule integrity.
Main Results:
- Suppression of microtubule dynamics impaired CCHFV biogenesis.
- Intact microtubules are essential for CCHFV entry and late-stage assembly/egress.
- Microtubule disruption reduced viral RNA levels and affected virus egress.
- CCHFV glycoprotein remained associated with the Golgi apparatus despite protein redistribution.
Conclusions:
- Microtubule dynamics are critical for multiple stages of the CCHFV life cycle.
- Targeting microtubule dynamics could be a strategy to control CCHFV infection.
- This study reveals novel insights into CCHFV-host cell interactions involving the cytoskeleton.
Abstract:
Following binding and entry many viruses exploit the host cell cytoskeleton to ensure intracellular transport, assembly or egress. For Crimean-Congo hemorrhagic fever virus (CCHFV), the causative agent of a severe hemorrhagic disease, virus-host interactions are poorly investigated. In this study we demonstrated that drug-induced suppression of microtubule dynamics and especially microtubule disassembly, impaired CCHFV biogenesis. Our results showed that intact microtubules were required early during virus internalization, and late, during virus assembly and egress. Furthermore, disruption of microtubules resulted in reduced levels of viral RNA while preservation of microtubule dynamics was most important during viral egress. Finally, although CCHFV proteins were redistributed in drug-treated cells, the glycoprotein remained associated with the Golgi apparatus, the organelle of virus budding. Taken together, our results suggest that manipulation of microtubules affects CCHFV entry, replication, assembly and egress.
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