Junin virus induces autophagy in human A549 cells

PEREZ VIDAKOVICS; ROMANOWSKI V; ARRIAS; URE AE; RICARDO M GOMEZ

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2019 vol. 14 p. 1 - 22

1932-6203

Autophagy, a highly regulated degradative process that promotes cellular homeostasis, isincreasingly recognised as a fundamental component of the cellular response against viralinfection. In this study, we investigated the role of autophagy during Junı´n virus (JUNV) multiplicationusing human A549 cells. We found that JUNV infection induces an increment ofthe LC3-II/LC3-I ratio, an accumulation of punctate pattern in RFP-LC3-transfected cellsand the colocalisation of viral nucleoprotein and LC3 protein, suggesting autophagosomeformation. JUNV infection also induced the degradation of the autophagy receptor p62, suggestingthat complete autophagic flux was triggered. In addition, we showed that inhibitionof autophagy with bafilomycin A1 or 3-methyladenine significantly reduces viral multiplication.Moreover, viral yield was increased when autophagy was induced using rapamycin.Furthermore, JUNV infection induced the colocalisation of p62, ATG16, RAB5, RAB7A andLAMP1 with the autophagosomal LC3 protein. That suggests that phagosomes undergo thematuration process during viral infection. Finally, we demonstrated that siRNA experimentstargeting essential autophagy genes (ATG5, ATG7 and Beclin 1) reduce viral protein synthesisand viral yield. Overall, our results indicate that JUNV activates host autophagymachinery enhancing its multiplication.Introduction