The host protein CLUH participates in the subnuclear transport of influenza virus ribonucleoprotein complexes

The nucleus is highly compartmentalized yet dynamic. Subnuclear functions are regulated by controlling the subnuclear localization of the nuclear proteins. Influenza viral ribonucleoprotein (vRNP) is replicated in the nucleus and then exported to the cytoplasm. However, the precise subnuclear localization and transport of vRNPs remain unclear. Here, we show that CLUH, a host protein whose cellular function is not well established, plays a key role in the subnuclear transport of vRNP. Viral PB2 and M1 induced CLUH translocation to the nucleoplasm and SC35-positive speckles, respectively, even though CLUH is usually cytoplasmic. CLUH depletion inhibited the translocation of M1 to SC35-positive speckles, but did not interfere with PB2 localization to the nucleoplasm and disrupted the subnuclear transport of vRNP, abolishing vRNP nuclear export without affecting viral RNA or protein expression. Our findings suggest that CLUH plays a role in the subnuclear transport of progeny vRNP. Influenza virus PB2 and M1 induce translocation of host protein CLUH from the cytoplasm to SC35-positive speckles in the nucleoplasm where it has a role in subnuclear transport of the viral ribonucleoprotein.