Activation of PI3K, Akt, and ERK during early rotavirus infection leads to V-ATPase-dependent endosomal acidification required for uncoating

• DOI: 10.1371/journal.ppat.1006820
• Publication Date: 2018-01-20T01:00:16Z
• Authors: Mahmoud Soliman; Ja-Young Seo; Deok-Song Kim; Ji-Yun Kim; Jun-Gyu Park; Mia Madel Alfajaro; Yeong-Bin Baek; Eun-Hyo Cho; Joseph Kwon; Jong-Soon Choi; Mun-Il Kang; Sang-Ik Park; Kyoung-Oh Cho
• Keywords: Immunoprecipitation

The cellular PI3K/Akt and/or MEK/ERK signaling pathways mediate the entry process or endosomal acidification during infection of many viruses. However, their roles in early events group A rotaviruses (RVAs) have remained elusive. Here, we show that late-penetration (L-P) human DS-1 and bovine NCDV RVA strains stimulate these very infection. Inhibition both significantly reduced production viral progeny due to blockage virus particles late endosome, indicating neither two is involved trafficking. immunoprecipitation assays using antibodies specific for pPI3K, pAkt, pERK subunit E V-ATPase co-immunoprecipitated complex with pERK. Moreover, Duolink proximity ligation assay revealed direct association molecules pERK, are V-ATPase-dependent acidification. Acidic replenishment medium restored uncoating cells pretreated inhibitors pathways, confirming above results. Isolated components outer capsid proteins, expressed as VP4-VP8* VP4-VP5* domains, VP7, activated pathways. Furthermore, psoralen-UV-inactivated CsCl-purified triple-layered triggered activation Our data demonstrate multistep binding proteins L-P cell surface receptors phosphorylates PI3K, Akt, ERK, which turn directly interact acidify endosome RVAs. This study provides a better understanding RVA-host interaction uncoating, importance development strategies aiming at controlling preventing infections.