The many faces of superinfection exclusion

Viral infections involve the constant production and release of viral particles (virions) to uninfected host cells and tissues. Viral superinfection exclusion (SIE) is a critical defense mechanism employed by viruses to prevent other virions from infecting the same host cell. This inhibition is typically exclusive to the same or closely related viruses (homologous SIE) but can also occur between unrelated viral species (heterologous exclusion). Many theories exist regarding the evolutionary function of SIE, with the strongest suggesting it is a means of preserving genomic integrity, sequestering limited cellular resources, or maximizing spread by preventing freshly produced virions from reinfecting their cell of origin. There are many “faces” to SIE involving the activity of viral proteins that interfere with various stages of infection, including attachment, entry, trafficking, gene expression, and genome replication. Some viruses, like poxviruses, HIV, and alphaherpesviruses, utilize multiple, often redundant, SIE strategies. Understanding the mechanisms of SIE is crucial for comprehending the pathogenesis and spread of many viral diseases. Continued research into the diverse mechanisms of SIE could lead to the development of novel, epitope independent antiviral therapies that exploit virally driven, virally derived mechanisms to provide host protection.