Members of Venezuelan Equine Encephalitis complex entry into host cells by clathrin-mediated endocytosis in a pH-dependent manner

GHIETTO, LUCIA MARIA; GIL, PEDRO IGNACIO; OLMOS QUINTEROS, PALOMA; GOMEZ, EMILIANO; PIRIS, FRANCO MARTIN; KUNDA, PATRICIA; CONTIGIANI, MARTA; PAGLINI, MARIA GABRIELA

Scientific Reports

Springer Nature

Año: 2022 vol. 12

Pixuna virus (PIXV) and Río Negro virus (RNV) are mosquito-borne alphaviruses belonging to theVenezuelan Equine Encephalitis (VEE) complex, which includes pathogenic epizootic and enzooticsubtypes responsible for life-threatening diseases in equines. Considering that the frst steps inviral infection are crucial for the efcient production of new progeny, the aim of this study was toelucidate the early events of the replication cycle of these two viruses. To this end, we used chemicalinhibitors and the expression of dominant-negative constructs to study the dependence of clathrinand endosomal pH on PIXV and RNV internalization mechanisms. We demonstrated that both virusesare internalized primarily via clathrin-mediated endocytosis, where the low pH in endosomes is crucialfor viral replication. Contributing knowledge regarding the entry route of VEE complex membersis important to understand the pathogenesis of these viruses and also to develop new antiviralstrategies.