Dengue virus infection alters 3' end processing of replicative-dependent histones

RITA VAZ DRAGO; BERTA POZZI; MARTIN GARCÍA SOLÁ; MARÍA FLORENCIA TORTI; ANDREA GAMARNIK ; CYBELE GARCÍA ; ANABELLA SREBROW

Puerto Varas

Conferencia; II Molecular Biosystems Conference - Eukaryotic Gene Regulation and Functional Genomics; 2019

Universidad Andrés Bello, Santiago, Chile - Pontificia Universidad Católica de Chile - Universidad Mayor, Santiago, Chile

According to World Health Organization, almost 400 million dengue infections occur every year, and the number of cases reported has been increasing during the last decades. Analysis of host gene expression profiles after infection of virus provides information about their pathogenic mechanisms. Recently, it has been shown that dengue virus is able to modulate the splicing pattern of infected cells through binding of the viral NS5 protein to several spliceosome components. Here we show that dengue virus can induce alternative polyadenylation of transcripts isolated from cultured human cells infected with this flavivirus. Particularly, we found that 3' end processing of replicative-dependent histone transcripts is affected upon dengue infection, leading to the production of longer transcripts that may escape the normal processing and become polyadenylated. Moreover, 3' end processing factors involved in maturation of replicative-dependent histone transcripts are downregulated as a consequence of dengue infection. Consistent with that, when infected with dengue virus, human cells display altered expression of factors involved in cell cycle regulation, suggesting that infection by dengue virus may induce defects in cell cycle progression.