Classical swine fever virus employs the PERK- and IRE1-dependent autophagy for viral replication in cultured cells.

Zhu, Erpeng; Wu, Huawei; Chen, Wenxian; Qin, Yuwei; Liu, Jiameng; Fan, Songqing; Ma, Shuaipeng; Wu, Keke; Mao, Qian; Luo, Chaowei; Qin, Yixian; Yi, Lin; Ding, Hongxing; Zhao, Mingqiu; Chen, Jinding

doi:10.1080/21505594.2020.1845040

Cited by 21 publications

(13 citation statements)

References 59 publications

(89 reference statements)

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“…The predominant localization of the granules in the perinuclear space may indicate the accumulation of chimeric glycoproteins in the endoplasmic reticulum and the Golgi apparatus during posttranslational modification (Fig 2 .A2). Noteworthy, E2 can be involved in the endoplasmic reticulum stress (ERS)mediated autophagy, induced by CSFV in the host cell for sustaining virus replication both in vivo and in vitro [21]. Besides, it has been shown that E2 can interact with a wide range of host proteins such as actin, thiredoxin, an-nexin 2, dynactin 6, mitogen-activated protein kinase 2, SERTA domain containing protein 1, etc.…”

Section: Resultsmentioning

confidence: 99%

Inverted terminal repeats from adeno-associated virus-2 enhance the expression of the chimeric E2 glycoprotein gene of classical swine fever virus

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Inverted terminal repeats from adeno-associated virus-2 enhance the expression of the chimeric E2 glycoprotein gene of classical swine fever virus

et al. 2021

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“…The replication of Kaposi’s sarcoma-associated herpesvirus (KSHV) depends on the activation of all three UPR sensors (3). Two investigations have shown that all three UPR signals are required for effective CSFV replication (37, 38). The activation of PERK and IRE1 increases the replication of porcine epidemic diarrhea virus (PEDV), but ATF6 has no effect on PEDV replication (39).…”

Section: Discussionmentioning

confidence: 99%

Emerging Evidence for Poxvirus-Mediated Unfolded Protein Response: Lumpy Skin Disease Virus Maintains Self-replication by Activating PERK and IRE1

Tan¹,

Liu²,

Yang³

et al. 2022

Preprint

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The cytoplasmic replication of poxviruses requires extensive protein synthesis, challenging the capacity of the endoplasmic reticulum (ER). However, the role of the ER in the life cycle of poxviruses is unclear. In this study, we demonstrate that infection with the lumpy skin disease virus (LSDV), a poxvirus, causes ER stress in vivo and in vitro, further facilitating the activation of the unfolded protein response (UPR). Although UPR activation aids in the restoration of the cellular environment, its significance in the LSDV life cycle remains unclear. Furthermore, the role of ER imbalance for viral replication is also unknown. We show that LSDV replication is hampered by an unbalanced ER environment. In addition, we verify that the LSDV replication depends on the activation of PERK-eIF2α and IRE1-XBP1 signaling cascades rather than ATF6, implying that global translation and XBP1 cleavage are deleterious to LSDV replication. Our findings suggest that LSDV engages all UPR signaling sensors, and that activation of PERK and IRE1 sensors is indispensable to maintaining its own replication.

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“…Also, autophagy is a key driver of malignant transformation in virus-related tumor development, which is selectively triggered during viral replication to increase the ability to live in a high-energy-required environment [12][13][14]. For instance, previous studies showed that classical swine fever virus [15] and bovine ephemeral fever virus [16] induce autophagy during viral replication, while inhibition of virus-induced autophagy with aspirin suppressed viral replication. Similarly, HPV also exploits the autophagic machinery for infection and proliferation of infected epithelial cells, although the role of autophagy appears to be less clear-cut as it can act as both tumor suppressor and a promoter [17].…”

Section: Introductionmentioning

confidence: 99%

Human Papillomavirus Type 16 Early Protein E7 Activates Autophagy through Inhibition of Dual-Specificity Phosphatase 5

Hua

Zheng

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Consistent high-risk human papillomavirus (HPV) infection leads to various malignant cancers. Autophagy can promote cancer progression by helping cancer cells survive under stress or induce oncogenic effects when mutations or abnormalities occur. Mitogen activated protein kinases (MAPKs) can transduce various external or intrinsic stimuli into cellular responses, including autophagy, and dual-specificity phosphates (DUSPs) contribute to the direct regulation of MAPK activities. Previously, we showed that expression of DUSP5 was repressed in HPV16 E7-expressing normal human epidermal keratinocytes (NHEKs). Here we show that clinical HPV16 E7-positive precancerous and cancerous tissues also demonstrate low DUSP5 levels compared with control tissues, indicating that the inverse correlation between HPV16 E7 and DUSP5 is clinically relevant. We furthermore investigated the autophagy response in both DUSP5-deficient and HPV16 E7-expressing NHEKs. Confocal microscopy and Western analysis showed induction of LC3-II levels, autophagosome formation and autophagy fluxes in DUSP5-deficient NHEKs. Furthermore, Western analysis demonstrated specific induction of phosphorylated ERK in DUSP5-deficient and HPV16 E7-expressing NHEKs, indicating that HPV16 E7-mediated repression of DUSP5 results in induced MAPK/ERK signaling. Finally, phosphorylated mTOR and ULK (S757) were reduced in DUSP5-deficient NHEKs, while phosphorylated ULK (S555) and AMPK were increased, thereby inducing canonical autophagy through the mTOR and AMPK pathways. In conclusion, our results demonstrate that HPV16 E7 expression reduces DUSP5 levels, which in turn results in active MAPK/ERK signaling and induction of canonical autophagy through mTOR and MAPK regulation. Given its demonstrated inverse correlation with clinical cancerous tissues, DUSP5 may serve as a potential therapeutic target for cervical cancer.

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Classical swine fever virus employs the PERK- and IRE1-dependent autophagy for viral replication in cultured cells.

Cited by 21 publications

References 59 publications

Inverted terminal repeats from adeno-associated virus-2 enhance the expression of the chimeric E2 glycoprotein gene of classical swine fever virus

Inverted terminal repeats from adeno-associated virus-2 enhance the expression of the chimeric E2 glycoprotein gene of classical swine fever virus

Emerging Evidence for Poxvirus-Mediated Unfolded Protein Response: Lumpy Skin Disease Virus Maintains Self-replication by Activating PERK and IRE1

Human Papillomavirus Type 16 Early Protein E7 Activates Autophagy through Inhibition of Dual-Specificity Phosphatase 5

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