Newcastle disease virus-induced autophagy mediates antiapoptotic signaling responses in vitro and in vivo

Abstract

In this study, we investigated the role of autophagy and apoptosis in Newcastle disease virus (NDV)-infected chicken cells and tissues. NDV-infected and starvation-induced chick embryo fibroblasts (CEF) cells showed higher autophagosome formation than mock-infected CEF cells on transmission electron microscopy. The NDV-infected CEF cells showed enhanced conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to LC3-II and degradation of p62/SQSTM1. The diminished conversion of LC3-I to LC3-II and cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in ultraviolet-inactivated NDV-infected cells suggested that autophagosome formation was necessary for NDV replication. Inhibition of autophagy by chloroquine (CQ) enhanced apoptosis resulting in increased cleavage of caspase 3 and PARP and AnnexinV/propidium iodide staining. Autophagy induction by rapamycin resulted in upregulation of all autophagy-related genes except Beclin 1, anti-apoptosis factors, and proinflammatory cytokines in the NDV-infected spleen and lung tissues. Subsequently, decreased apoptosis was observed in NDV-infected spleens and lungs than mock-infected organs. The pan-caspase inhibitor ZVAD-FMK promoted conversion of LC3-I to LC3-II, the degradation of p62/SQSTM1, NDV replication and cell viability by inhibiting apoptosis. Our study demonstrates that apoptosis inhibition enhances autophagy and promoted cell survival and NDV replication.

Genetic alteration profiling of patients with resected squamous cell lung carcinomas

“…Mu et al [35] found that high expression of PD-L1 in lung cancer may contribute to poor prognosis, however, Brahmer et al [36] reported that the expression of PD-L1 was neither prognostic nor predictive of benefit. Böger et al [37] found that high expression of PD-L1/PD-1 was associated with a significantly better outcome, and PD-L1 was an independent survival prognosticator in gastric cancer. Simlar to Böger et al's report, we also found the patients with positive expression of PD-L1 had a significantly longer DFS, and it was an independent favorable prognostic factor for DFS in SqCLC.…”

Autophagy induction by the pathogen receptor NECTIN4 and sustained autophagy contribute to peste des petits ruminants virus infectivity

“…Accordingly, pathogens have developed strategies to avoid or hijack autophagy for their own benefit. An increasing number of viruses belonging to the family Paramyxoviridae have been reported to utilize an autophagic mechanism to facilitate replication, including MeV [33], PPRV [36,37], human respiratory syncytial virus [57], CDV [35] and Newcastle disease virus [58]. Among these pathogens, attenuated MeV induces two successive waves of autophagy via distinct molecular pathways [33].…”

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

“…In contrast, low basal levels of LC3-II were present in mock-infected cells, indicating that basal autophagy in normal EECs was essential for maintaining homeostasis. Recent studies show that several members of the Paramyxoviridae family, including MeV [16], human respiratory syncytial virus [52], canine distemper virus [53] and Newcastle disease virus [35], can utilize an autophagy mechanism to facilitate replication. To further determine what role autophagy plays in the replication of PPRV, we examined viral replication ability by exposing EECs to rapamycin, an inducer of autophagy that specifically inhibits the action of mTOR [54].…”

“…Autophagy is involved in the apoptosis and death of T lymphocytes in the spleen of pigs infected with CSFV [34]. Moreover, autophagy triggered by genotype VII Newcastle disease virus infection was essential for viral replication, NDV-induced apoptosis, and cell survival in chicken cells and tissues [35]. …”