Divergent Roles of Autophagy in Virus Infection

Chiramel, Abhilash I.; Brady, Nathan R.; Bartenschlager, Ralf

A number of studies have convincingly demonstrated that autophagy can influence the presentation of viral antigens on MHC-I and MHC-II [66] . Studies with HSV-1 showed that at early time points after infection, autophagy is not required for viral antigen processing and presentation of MHC-I peptides, but comes into play at late stage of infection [67] . However, it remains unknown how degradation of HSV-1 particles by the autophagosome results in the presentation of viral antigens to ER localized MHC-I molecules. In the case of Epstein Barr virus (EBV), the viral protein EBNA1 is targeted to MHC-II compartments via autophagic uptake and fusion of autophagosomes with these compartments [68] . Inhibition of autolysosomal acidification resulted in enrichment of EBNA1-positive autophagosomes, and knock-down of Atg12 rendered the cells unable to stimulate MHC-II-dependent activation of T-cells [69] . Importantly, already under normal conditions and in the absence of viral infection, autophagy was required for the consecutive delivery of antigens to MHC-II molecules, arguing for a crucial role of autophagy in MHC-II presentation of antigens in vivo [70] . Furthermore, by fusing the matrix protein of influenza virus to LC3, an increased MHC-II activation of CD4+ T-cells was observed, thus revealing an unexplored strategy for vaccine development [70] .