Nuclear trafficking of proteins from RNA viruses: Potential target for antivirals?

A key aspect of the infectious cycle of many viruses is the transport of specific viral proteins into the host cell nucleus to perturb the antiviral response. Examples include a number of RNA viruses that are significant human pathogens, such as human immunodeficiency virus (HIV)-1, influenza A, dengue, respiratory syncytial virus and rabies, as well agents that predominantly infect livestock, such as Rift valley fever virus and Venezuelan equine encephalitis virus. Inhibiting the nuclear trafficking of viral proteins as a therapeutic strategy offers an attractive possibility, with important recent progress having been made with respect to HIV-1 and dengue. The results validate nuclear protein import as an antiviral target, and suggest the identification and development of nuclear transport inhibitors as a viable therapeutic approach for a range of human and zoonotic pathogenic viruses.

► Many RNA viruses that replicate in the cytoplasm require the nuclear transport of one or more proteins.
► Blocking the transport of these components into or out of the nucleus can reduce viral replication.
► Inhibition of nuclear trafficking of RNA viral proteins represents a novel antiviral strategy.
► Targeting the interface between viral and host cell proteins should improve drug specificity without toxicity.