Autophagy Promotes Porcine Parvovirus Replication and Induces Non-Apoptotic Cell Death in Porcine Placental Trophoblasts

Zhang, Xiujuan; Xiong, Yingli; Zhang, Jie; Shao, Ting; Chen, Songbiao; Miao, Bichen; Wang, Zhenyu; Du, Qian; Huang, Yong; Tong, Dewen

doi:10.3390/v12010015

Cited by 12 publications

(9 citation statements)

References 43 publications

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“…P1400, Solarbio, CHN) at 37 °C in an incubated with 5% CO 2 atmosphere. PPV China-XY strain (MK993540) was propagated as previously described [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…AMPK is a negative regulator of mTORC1, which can suppress mTORC1 by activating tuberous sclerosis complex 2 (TSC2) or phosphorylating the regulatory-associated protein of mTORC1 (Raptor) [ 21 , 22 ]. Our recent study showed that PPV infection induces autophagy in PTCs [ 23 ]. Therefore, we were interested in determining whether mTORC1 is involved in PPV-induced autophagy and whether PPV-induced autophagy occurs via an AMPK-dependent mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Porcine parvovirus triggers autophagy through the AMPK/Raptor/mTOR pathway to promote viral replication in porcine placental trophoblasts

Zhang

Shao

et al. 2022

Vet Res

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Autophagy has been demonstrated to play important roles in the infection and pathogenesis of many viruses. We previously found that porcine parvovirus (PPV) infection can induce autophagy in porcine placental trophoblast cells (PTCs), but its underlying mechanism has not yet been fully revealed. In this study, we showed that PPV infection inhibited the activation of mTORC1 and promoted the expression of Beclin 1 and LC3II in PTCs. Treatment with a mTOR activator inhibited the expression of Beclin 1 and LC3II, as well as autophagy formation, and reduced viral replication in PPV-infected PTCs. Furthermore, we found that inhibition of AMPK expression, but not the inhibition of PI3K/Akt, p53, or MAPK/ERK1/2 pathway activation, can significantly increase mTOR phosphorylation in PPV-infected PTCs. Then, we found that the regulation of mTOR phosphorylation by AMPK was mediated by Raptor. AMPK expression knockout inhibited the activation of Raptor, decreased the expression of Beclin 1 and LC3II, suppressed the formation of autophagosomes, and reduced viral replication during PPV infection. Together, our results showed that PPV infection induces autophagy to promote viral replication by inhibiting the activation of mTORC1 through activation of the AMPK/Raptor pathway. These findings provide information to understand the molecular mechanisms of PPV-induced autophagy.

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“…P1400, Solarbio, CHN) at 37 °C in an incubated with 5% CO 2 atmosphere. PPV China-XY strain (MK993540) was propagated as previously described [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Porcine parvovirus triggers autophagy through the AMPK/Raptor/mTOR pathway to promote viral replication in porcine placental trophoblasts

Zhang

Shao

et al. 2022

Vet Res

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“…Specific siRNAs used to silence Akt, p38 MAPK, JNK, ERK, AMPK, PKCδ were referred to in our previous study[ 36 , 63 ]. HDAC6 (GenBank: XM_003360315.5) and AMPK (GenBank: NM_001167633.1) siRNAs were designed (HDAC6 siRNA: 5′-GGAGGAGCUUAUGUUGGTT-3′; AMPK siRNA: 5′-GCUUGCCAAAGGAAUGATT-3′).…”

Section: Methodsmentioning

confidence: 99%

PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

Wang

Chen

et al. 2021

PLoS Pathog

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Viruses use diverse strategies to impair the antiviral immunity of host in order to promote infection and pathogenesis. Herein, we found that PCV2 infection promotes the infection of DNA viruses through inhibiting IFN-β induction in vivo and in vitro. In the early phase of infection, PCV2 promotes the phosphorylation of cGAS at S278 via activation of PI3K/Akt signaling, which directly silences the catalytic activity of cGAS. Subsequently, phosphorylation of cGAS at S278 can facilitate the K48-linked poly-ubiquitination of cGAS at K389, which can been served as a signal for recognizing by the ubiquitin-binding domain of histone deacetylase 6 (HDAC6), to promote the translocation of K48-ubiquitinated-cGAS from cytosol to autolysosome depending on the deacetylase activity of HDAC6, thereby eventually resulting in a markedly increased cGAS degradation in PCV2 infection-induced autophagic cells relative to Earle’s Balanced Salt Solution (EBSS)-induced autophagic cells (a typical starving autophagy). Importantly, we found that PCV2 Cap and its binding protein gC1qR act as predominant regulators to promote porcine cGAS phosphorylation and HDAC6 activation through mediating PI3K/AKT signaling and PKCδ signaling activation. Based on this finding, gC1qR-binding activity deficient PCV2 mutant (PCV2RmA) indeed show a weakened inhibitory effect on IFN-β induction and a weaker boost effect for other DNA viruses infection compared to wild-type PCV2. Collectively, our findings illuminate a systematic regulation mechanism by which porcine circovirus counteracts the cGAS-STING signaling pathway to inhibit the type I interferon induction and promote DNA virus infection, and identify gC1qR as an important regulator for the immunosuppression induced by PCV2.

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“…PPV XY strain (Genbank: MK993540) was propagated in PK-15 cells. The crude PPV preparation was purified using ultracentrifugation over sucrose cushions (2 mL of 50% sucrose plus 2 mL of 20% sucrose) by Optima XPN-100 Ultracentrifugation with a SW 41 Ti rotor, at 200 000 g for 2 h. Virus titers in the culture supernatants were determined by the Reed-Muench method [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation

Chen

Miao

Chen

et al. 2021

Vet Res

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Porcine Parvovirus (PPV), a pathogen causing porcine reproductive disorders, encodes two capsid proteins (VP1 and VP2) and three nonstructural proteins (NS1, NS2 and SAT) in infected cells. The PPV NS2 mRNA is from NS1 mRNA after alternative splicing, yet the corresponding mechanism is unclear. In this study, we identified a PPV NS1 mRNA binding protein SYNCRIP, which belongs to the hnRNP family and has been identified to be involved in host pre-mRNA splicing by RNA-pulldown and mass spectrometry approaches. SYNCRIP was found to be significantly up-regulated by PPV infection in vivo and in vitro. We confirmed that it directly interacts with PPV NS1 mRNA and is co-localized at the cytoplasm in PPV-infected cells. Overexpression of SYNCRIP significantly reduced the NS1 mRNA and protein levels, whereas deletion of SYNCRIP significantly reduced NS2 mRNA and protein levels and the ratio of NS2 to NS1, and further impaired replication of the PPV. Furthermore, we found that SYNCRIP was able to bind the 3′-terminal site of NS1 mRNA to promote the cleavage of NS1 mRNA into NS2 mRNA. Taken together, the results presented here demonstrate that SYNCRIP is a critical molecule in the alternative splicing process of PPV mRNA, while revealing a novel function for this protein and providing a potential target of antiviral intervention for the control of porcine parvovirus disease.

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Autophagy Promotes Porcine Parvovirus Replication and Induces Non-Apoptotic Cell Death in Porcine Placental Trophoblasts

Cited by 12 publications

References 43 publications

Porcine parvovirus triggers autophagy through the AMPK/Raptor/mTOR pathway to promote viral replication in porcine placental trophoblasts

Porcine parvovirus triggers autophagy through the AMPK/Raptor/mTOR pathway to promote viral replication in porcine placental trophoblasts

PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation

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