has been observed in both ticks and mammals experimentally infected with more than one thogotovirus, but its significance in natural infections is unknown. Viral proteins The genome encodes 7–9 proteins, including the trimeric RNA polymerase enzyme (PA, PB1, PB2) and the structural proteins nucleoprotein (NP), which binds the viral genome; matrix protein (M1), which lines the envelope; and an envelope glycoprotein (GP), which acts as the virus receptor. The thogotovirus glycoprotein is not similar to the influenza virus glycoproteins (haemagglutinin and neuraminidase), and instead shows some similarities with the gp64 glycoprotein of baculoviruses, which infect insects. It also has some similarity with the haemagglutinin of Quaranfil virus of the related genus of tick-transmitted orthomyxoviruses Quaranjavirus. The mechanism by which thogotoviruses gained a baculovirus-like glycoprotein is unknown. Pat Nuttall and colleagues have speculated that the acquisition enabled these viruses to infect ticks. This apparent receptor specificity for arthropod cells does not prevent most thogotoviruses from infecting vertebrates. The thogotovirus glycoprotein is classified as a class III or γ penetrene, lacking the fusion peptide present in influenza haemagglutinin (a class I or α penetrene). THOV and JOSV also encode the protein M-long (ML), which counters the host's innate immunity, in particular by suppressing the production of interferon. This immune evasion is important for the virus to infect systemically in vertebrates, but is unnecessary in arthropods, which lack the interferon response. The mechanism of action of ML is completely different from the equivalent protein in influenza viruses (NS1). As in all orthomyxoviruses, the largest three segments (1–3) encode the three subunits of the RNA polymerase. In thogotoviruses, segment 4 encodes the glycoprotein and segment 5 the nucleoprotein. The messenger RNA (mRNA) from segment 6 can be spliced to encode the matrix protein or unspliced to encode ML, which has 38 additional amino acids at its C-terminus. No product has yet been identified for the seventh segment, observed in DHOV. Life cycle The receptor on the vertebrate host cell is sialic acid, which is bound by the viral glycoprotein. Entry is by endocytosis, with fusion of the viral and cell membranes occurring once the vesicle is acidified. In common with other orthomyxoviruses, viral transcription and replication both occur in the cell nucleus. In some members of the genus, replication has been shown to be sensitive to the Mx1/MxA protein, which is induced in mice and humans in response to interferon. In one study, this