Evasion of the immune system
Many viruses have mechanisms to inhibit, suppress or evade the immune response in order to continue replication and transmission. These include inhibition of antigen processing, suppression of interferon production, inhibition of phagocytes, and reduced immunogenicity, alteration of lymphocyte traffic, effects on cellular modulators, depression of Complement activity, resistance to the immune effectors, and rapidly appearing antigenic variation. Many viruses use several different mechanisms together.
Most of the Herpesviridae of course escape the immune system while latent in their host and several have other mechanisms that act during acute replication. Epstein–Barr virus (EBV) inhibits antigen presentation to immune cells and interferon production through expression of a protein similar to interleukin 10, an inhibitory cytokine. HSV can interfere with NK cell function or even kill these cells and CMV suppresses NK cell lysis by mimick- ing MHC proteins. Both HSV and EBV structural proteins interfere with the Complement cascade and an HSV structural protein on infected cell surfaces prevents Complement fixation or opsonization by phagocytes. The Adenoviridae and Poxviridae (such as vac- cinia virus) also interfere with antigen presentation by down-regulating the expression of MHC type I protein and are capable of inhibiting the antiviral mechanism of interferon in cells. The high mutation rate of many RNA viruses gives rise to alterations in antigenic molecules such that they are no longer recognized by the circulating immune cells and antibodies.
This is evident during the long-term infection of HIV within a host and is also seen at the population level in the influenza virus. As this virus undergoes constant rep- lication within different hosts across a population, gradual antigenic changes result from mutations, causing antigenic drift. This accounts for the yearly recurrence of influenza across the globe, and the need for new vaccine formulations each year, as the mutations change the viral antigens sufficiently that immunological memory does not recognize them. Occasionally, larger genetic changes occur, known as antigenic shift, where a com- plete genomic segment is altered as a result of a process known as reassortment. The influenza a virus that infects humans can also infect pigs and birds, where it may invade cells that also harbor porcine or avian influenza viruses. One or more of the genomic segments from these viruses may be packaged within a virion that otherwise comprises influenza A virus proteins and genomic segments. When these segments encode for the strongly immunogenic proteins such as HA or NA, the resulting new virus may be capa- ble of replication in previously immune hosts, as the immune memory to influenza virus HA and NA molecules cannot recognize the new antigens. On several occasions during history, antigenic shift has led to severe influenza pandemics that have spread devastating illness across the globe.