IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection
Gloria Griffante, Weronika Hewelt-Belka, Camilla Albano, Francesca Gugliesi, Selina Pasquero, Sergio Fernando Castillo Pacheco, Greta Bajetto, Paolo E. Porporato, Erica Mina, Marta Vallino, Christian Krapp, Martin R. Jakobsen, John G. Purdy, Jens von Einem, Santo Landolfo, Valentina Dell’Oste, Matteo Biolatti
Abstract
Human cytomegalovirus (HCMV) gathers all the substrates and enzymes necessary for the assembly of new virions from its host cell. For instance, HCMV is known to induce cellular metabolism of infected cells to favor virion assembly. Cells are, however, equipped with a first-line defense represented by restriction factors (RFs), which after sensing viral DNA can trigger innate and adaptive responses, thereby blocking HCMV replication. One such RF is IFN-γ-inducible protein 16 (IFI16), which we have shown to downregulate viral replication in human fibroblasts. Thus, we asked whether IFI16 would also play a role in preserving cellular metabolism upon HCMV infection. Our findings highlight an unprecedented role of IFI16 in opposing the metabolic changes elicited by HCMV, thus revealing new promising targets for antiviral therapy.