Zika virus inhibits eIF2α-dependent stress granule assembly

Zika virus (ZIKV), a member of the Flaviviridae family, is the most recent emerging arbovirus with pandemic potential.During infection, viruses trigger the host cell stress response, leading to changes in RNA translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (SGs).Several reports demonstrate that flaviviruses modulate the assembly of stress granules (SG).As an emerging pathogen, little is known however about how ZIKV modulates the host cell stress response.In this work, we investigate how ZIKV modulates SG assembly.We demonstrate that ZIKV negatively impacts SG assembly under oxidative stress conditions induced by sodium arsenite (Ars), a treatment that leads to the phosphorylation of eIF2α.By contrast, no measurable difference in SG assembly was observed between mock and ZIKV-infected cells treated with sodium selenite (Se) or Pateamine A (PatA), compounds that trigger eIF2α-independent SG assembly.Interestingly, ZIKV infection markedly impaired the phosphorylation of eIF2α triggered in Ars-treated infected cells, and the abrogation of SG assembly in ZIKV-infected cells is, at least in part, dependent on eIF2α dephosphorylation.These data demonstrate that ZIKV elicits mechanisms to counteract host anti-viral stress responses to promote a cellular environment propitious for viral replication. Author summaryZika virus (ZIKV) is transmitted to humans primarily through mosquito bites, but there have also been cases of sexual, perinatal, and suspected blood transfusion transmission.It has been associated with fetal malformations and neurological disorders in adults.The rising concern about this pathogen led the World Health Organization to declare it as a public health emergency of international concern regarding neurological disorders.There is an urgent global scientific effort underway to better understand ZIKV biology and define interactions that occur between the virus and the host cell.