Restriction Factors Against Human CMV

Abstract

Cellular proteins called 'restriction factors' (RFs) form an important component of the innate immune response to viral replication. However, viruses have learned how to antagonize RFs through mechanisms that are specific for each virus. Here, we summarize the general hallmarks of RFs before going on to discuss the specific strategies recruited by some key RFs that strive to hold human CMV (HCMV) infection back, as well as the counter-restriction mechanisms employed by the virus to overcome this innate defense. Such RFs include the cellular constituents of nuclear domain 10 (ND10), and IFI16, a nuclear member of the PYHIN protein family. Viral regulatory proteins, such as IE1 or pp71, try to oppose the ND10-induced blockade of virus replication by either modifying or disrupting this RF. IFI16, on the other hand, inhibits virus DNA synthesis by downregulating the transcription of viral gene UL54; the intruding virus attempts to antagonize IFI16 by mislocalizing it from the nucleus to the cytoplasm via the action of viral protein UL97. Finally, we consider how Viperin, a RF initially thought to inhibit HCMV maturation late during infection, has actually been demonstrated to enhance virus maturation by increasing lipid metabolism and enhancing virus envelopment.