Impact of dengue virus on the expression of PML mRNA isoforms

GAIOLI, NICOLAS; GARCIA, CYBELE; SREBROW, ANABELLA

Rosario

Congreso; LIX Annual Meeting SAIB 2023; 2023

SAIB

Our laboratory seeks to understand how dengue virus infection modulates host cell gene expression. We have focused on the action of this virus on promyelocytic leukemia protein (PML) pre-mRNA processing and post-translational regulation of PML protein variants. Although the extensive literature available so far only refers to alternative splicing as the source for PML isoforms, a thorough analysis indicates that they are generated by the combination of alternative splicing and alternative polyadenylation. The PML gene is not only considered an ISG (interferon stimulated gene), induced during the innate immune response, but also certain PML protein isoforms have been described as viral restriction factors. In particular, PML III and IV limit dengue virus replication in human cell lines. Results from our group show that infection with this virus differentially alters the expression of PML isoforms, significantly decreasing the levels of PML IV mRNA at early time points and limiting the increase of this transcript during the process of viral proliferation, in contrast to what we observed for the other PML mRNA variants.Considering the antiviral role of PML IV protein mentioned above, this regulatory phenomenon could be part of the multiple strategies deployed by dengue virus to counteract or evade the innate cellular immune response. We are exploring the molecular mechanism and the viral and host cell components responsible for the differential regulation of PML IV mRNA expression upon infection, giving special attention to the hitherto overlooked alternative polyadenylation of PML pre-RNA.