Microtubule-dependent and microtubule-independent steps in Crimean-Congo hemorrhagic fever virus replication cycle.
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.
Simon
Melinda
M
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. melinda.simon@smi.ki.se
Johansson
Cecilia
C
Lundkvist
Ake
A
Mirazimi
Ali
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000235:genetics / Q000502:physiology*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D050257:Tubulin Modulators / Q000494:pharmacology; D014709:Vero Cells; D053586:Virus Internalization; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D012367:RNA, Viral; D050257:Tubulin Modulators; D017239:Paclitaxel; D015739:Nocodazole