Autophagic regulation of CD8+ T cell metabolic reprogramming defines acute and latent phases of cytomegalovirus infection in vivo.

Understanding the immunoregulatory mechanism during cytomegalovirus (CMV) infection may help to combat CMV reactivation in immunocompromised or immunosuppressed individuals. Here we developed a CMV infection model in immunocompetent Sprague Dawley (SD) rats with Priscott strain and explored the cross-talk between autophagic dynamics and metabolism alterations in CD8+ T cells post infection. We previously found that primary CMV infection induced a remarkable increase of CD8+ T cells which reached the peak around week 3 and returned to pre-inoculation status since week 6 post viral infection. In this study, our results demonstrated that the autophagic activity of CD8+ T cells was augmented at week 3 while decreased at week 6, which was closely associated with the up- (week 3 and 4) or down-regulation (since week 6) of metabolic markers ENTPD1 and SLC27A2. Furthermore, the in vitro study showed that the levels of these metabolic markers in rat splenocytes were modulated by autophagy inhibitors and enhancers. Our study indicated that the dynamic alterations of autophagy exerted a critical role in regulating the metabolic adaptation of CD8+ T cells during CMV infection process, and provides an ideal animal model for further research on the pathological mechanisms based on CMV latency.