Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5

Brisse, Morgan; Ly, Hinh

The comparative abilities for DI particles vs. infectious virions to activate RIG-I and MDA5 have important implications for understanding viral pathogenesis and for vaccine development. There is a burgeoning interest in this regard, especially in populations which are typically more challenging to achieve successful preventative vaccination, such as elderly populations with IAV vaccination (213) . Elderly populations in general do not develop as strong of memory immune responses to vaccines as their younger counterparts (214) (215) (216) (217) and have been found to have decreased RIG-I mediated IFN1 signaling (218) . Correspondingly, the influenza vaccine has been shown to decrease in effectiveness in older populations as the influenza season progresses (219) . A DI-vaccine that strongly activates innate immune cells and increases the adaptive immune response could therefore potentially boost the immune responses to vaccines in more vulnerable populations. Additionally, DI particles have shown to be an important contributor of viral persistence (200, 220, 221) . This raises the question of whether a viral infection may alternate between producing primarily infectious virions which eventually activates the innate immune response and producing primarily DI particles which requires less cellular activity but may initiate an even stronger innate immune response (222) (223) (224) . Taken altogether, DI particles provide yet another layer of distinction between RIG-I and MDA5 in terms of how each recognizes different species of dsRNA.