Evasion of innate and adaptive immune responses by influenza A virus

Abstract

Host organisms have developed sophisticated antiviral responses in order to defeat emerging influenza A viruses (IAVs). At the same time IAVs have evolved immune evasion strategies. The immune system of mammals provides several lines of defence to neutralize invading pathogens or limit their replication. Here, we summarize the mammalian innate and adaptive immune mechanisms involved in host defence against viral infection and review strategies by which IAVs avoid, circumvent or subvert these mechanisms. We highlight well-characterized, as well as recently described features of this intriguing virus-host molecular battle.

Figure 1. Viral evasion strategies in infected and bystander cells

(A) IAV NS1 limits RIG-I activation by interference with TRIM25. (B) 5′m7G-cap snatching by the IAV polymerase complex and interference of NS1 with CPSF30 result in host protein synthesis shut down. (C) Upregulation of SOCS3 limits IFN type I signaling in host cells. (D) IAV NS1 directly antagonizes ISGs.

Figure 2. Genetic variability of IAV allows efficient escape from the host immune system

(A) Antigenic drift: The high mutation rate of IAV (strain X) results in the establishment of antigenically new IAV (strain X*, mutations indicated by red circles) and allows the virus to escape from the adaptive host response and antiviral drugs. (B) Antigenic shift: Genetic re-assortment in double infected cells creates IAVs with a completely new surface structure. These viruses can have pandemic potential due to a lack of preexisting immunity in the host population.