AUTHOR=Salvia Rosanna , Nardiello Marisa , Scieuzo Carmen , Scala Andrea , Bufo Sabino A. , Rao Asha , Vogel Heiko , Falabella Patrizia 

TITLE=Novel Factors of Viral Origin Inhibit TOR Pathway Gene Expression

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01678

DOI=10.3389/fphys.2018.01678

ISSN=1664-042X

ABSTRACT=<p>Polydnaviruses (PDVs) are obligate symbionts of endoparasitoid wasps, which exclusively attack the larval stages of their lepidopteran hosts. The Polydnavirus is injected by the parasitoid female during oviposition to selectively infect host tissues by the expression of viral genes without undergoing replication. <italic>Toxoneuron nigriceps</italic> bracovirus (<italic>Tn</italic>BV) is associated with <italic>Toxoneuron nigriceps</italic> (Hymenoptera: Braconidae) wasp, an endoparasitoid of the tobacco budworm larval stages, <italic>Heliothis virescens</italic> (Lepidoptera: Noctuidae). Previous studies showed that <italic>Tn</italic>BV is responsible for alterations in host physiology. The arrest of ecdysteroidogenesis is the main alteration which occurs in last (fifth) instar larvae and, as a consequence, prevents pupation. <italic>Tn</italic>BV induces the functional inactivation of <italic>H. virescens</italic> prothoracic glands (PGs), resulting in decreased protein synthesis and phosphorylation. Previous work showed the involvement of the PI3K/Akt/TOR pathway in <italic>H. virescens</italic> PG ecdysteroidogenesis. Here, we demonstrate that this cellular signaling is one of the targets of <italic>Tn</italic>BV infection. Western blot analysis and enzyme immunoassay (EIA) showed that parasitism inhibits ecdysteroidogenesis and the phosphorylation of the two targets of TOR (4E-BP and S6K), despite the stimulation of PTTH contained in the brain extract. Using a transcriptomic approach, we identified viral genes selectively expressed in last instar <italic>H. virescens</italic> PGs, 48 h after parasitization, and evaluated expression levels of PI3K/Akt/TOR pathway genes in these tissues. The relative expression of selected genes belonging to the TOR pathway (<italic>tor</italic>, <italic>4e-bp</italic>, and <italic>s6k</italic>) in PGs of parasitized larvae was further confirmed by qRT-PCR. The down-regulation of these genes in PGs of parasitized larvae supports the hypothesis of <italic>Tn</italic>BV involvement in blocking ecdysteroidogenesis, through alterations of the PI3K/Akt/TOR pathway at the transcriptional level.</p>