Cross-talking between autophagy and viral infection in mammalian cells

doi:10.1007/s11515-010-0760-8

Front Biol

2010, Vol. 5

Issue (6) : 507-515 https://doi.org/10.1007/s11515-010-0760-8

REVIEW

Cross-talking between autophagy and viral infection in mammalian cells

Hongya HAN, Lishu ZHANG(

), Xinxian DAI, Yanpeng ZHENG

College of Life Sciences & Bioengineering, Beijing Jiaotong University, Beijing 100044, China

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Abstract

Autophagy is a cellular process in degradation of long-lived proteins and organelles in the cytosol for maintaining cellular homeostasis, which has been linked to a wide range of human health and disease states, including viral infection. The viral infected cells exhibit a complicated cross-talking between autophagy and virus. It has been shown that autophagy interacts with both adaptive and innate immunity. For adaptive immunity, viral antigens can be processed in autophagosomes by acidic proteases before major histocompatibility complex (MHC) class II presentation. For innate immunity, autophagy may assist in the delivery of viral nucleic acids to endosomal TLRs and also functions as a part of the TLR-or-PKR-downstream responses. Autophagy was also reported to suppress the magnitude of host innate antiviral immunity in certain cases. On the other hand, viruses has evolved many strategies to combat or utilize the host autophagy for their own benefit. In this review we discussed recent advances toward clarifying the cross-talking between autophagy and viral infection in mammalian cells.

Keywords cross-talking autophagy viral infection

Corresponding Author(s): ZHANG Lishu,Email:lshzhang@bjtu.edu.cn

Issue Date: 01 December 2010

Cite this article:

Hongya HAN,Lishu ZHANG,Xinxian DAI, et al. Cross-talking between autophagy and viral infection in mammalian cells[J]. Front Biol, 2010, 5(6): 507-515.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-010-0760-8
https://academic.hep.com.cn/fib/EN/Y2010/V5/I6/507

Fig.1 The cross-talking between viruses and host cells. A: Beclin1 is a component PI3K/Beclin1 complex which acts an important role in the initial stage of autophagy. UVRAG is a part of the PI3K/Beclin1 complex and representing an important signaling checkpoint in autophagy, while BCL-2 is able to inhibit autophagy by interacting with Beclin 1 as a negative regulator. It is because the essential roles of PI3K/Beclin1 complex, several viruses evolve some strategies to combat or employ it for their own benefits. HSV-1 expresses protein ICP34.5, HIV-1 has Nef, Kaposi's sarcoma-associated herpesvirus (KSHV) produces vBCL-2 and the murine γ-herpesvirus 68 encodes protein M11, as well as HBV express protein HBx to suppress autophagy by blocking the Beclin1. B: mTOR is known as the key down-regulator of autophagy induction, which can be inhibited by rapamycin and activated by amino acids. Class I PI3K/Akt lies on the upstream of mTOR and acts positively on it to inhibit autophagy, whereas the phosphatase and tension homolog (PTEN) acts antagonistically to the class I PI3K to induce autophagy indirectly. Besides, the ULK-Atg13-FIP200 complexe is a direct target of mTOR and important regulator of autophagy in response to mTOR signaling. Additionally, mTOR activity inhibits p73, which is the inducer of cellular autophagy, and in TNFα-treated cell, mTOR is necessary for NF-κB activation mediated repression of autophagy. In HCMV infected cells, mTOR can be activated to suppress autophagy for its own benefits. C: When viruses replicating in cells, the viral dsRNA activates PKR to phosphorylate eIF2α and then mediate viruses degradation through autophagy. However, HSV-1 has possibility encoding ICP34.5 to suppress cellular autophagy by dephosphorylating eIF2α in PKR pathway. In pDCs, the autophagic vesicles can wrap the replication intermediate of escaped VSV in cytoplasmic and then fuse with endosome who contain TLR7 to recognize viral replication intermediate to produce IFN- α. As we know, the viral dsRNA also stimulates IFN-α production via RIG-1 and ISP-1. Interestingly, in mouse embryonic fibroblasts (MEFs), the IFN-α production can be down-regulated in response to VSV by Atg5-Atg12 direct association with both RIG-I and IPS-1 through the caspase recruitment domains. For adaptive immunity, autophagy can deliver antigens into autophagosomes for processing by acidic proteases before MHC class II presentation. For example, autophagy helps presentation of endogenous EBNA-1 to T cells in EBV infected cells. D: Besides, TLR3, TLR4 and TLR7 are able to induce autophagy in certain cells. MHV, Poliovirus and CVB3 as well as HCV are capable inducing autophagosomes to generate sites and support their replication. Besides, HCV and CVB3 can suppress autophagic protein degradation by blocking the fusion of autophagosome and lysosome. Certain viruses such as enterovirus 71, influenza A virus, BVDV, human parvovirus B19 and dengue virus-2 are able to activate autophagy to enhance the efficiency of viral replication, but detail mechanisms are still unclear. More interestingly, Env of HIV is able to induce autophagy and accumulate the Beclin 1 in uninfected cells via CXCR4

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