Involvement of a tick-borne orthomyxovirus matrix protein in vRNP nuclear export

Dhori virus (DHOV) is a pathogenic tick-borne virus in the genus <i>Thogotovirus</i>, in the family Orthomyxoviridae. Despite evidence of DHOV exposure in various mammals, including humans, its basic biology is not well understood. We investigated how DHOV's progeny genome and protein complexes-viral ribonucleoprotein complexes (vRNPs)-are transported out of the nucleus. Our findings show that DHOV, like the influenza viruses, uses the cellular protein chromosomal maintenance protein 1 (CRM1) for vRNP export. We found that chemically inhibiting CRM1 completely blocked DHOV vRNP export, preventing the production of progeny viruses from infected cells. Screening of all known DHOV proteins revealed that the matrix protein, which forms the virus' scaffold, interacted with CRM1, suggesting it may link CRM1 to the vRNPs. These results advance our understanding of DHOV replication and suggest that chemically inhibiting vRNP export could be a way to treat thogotovirus infections.