The machinery for endocytosis of epidermal growth factor receptor coordinates the transport of incoming hepatitis B virus to the endosomal network

Iwamoto, Masashi; Saso, Wakana; Nishioka, Kazane; Ohashi, Hirofumi; Sugiyama, Ryuichi; Ryo, Akihide; Ohki, Mio; Yun, Ji-Hye; Park, Sam-Yong; Ohshima, Takayuki; Suzuki, Ritsuro; Aizaki, Hideki; Muramatsu, Masamichi; Matano, Tetsuro; Iwami, Shingo; Sureau, Camille; Wakita, Takaji; Watashi, Koichi

doi:10.1016/s0021-9258(17)49936-4

Cited by 46 publications

(21 citation statements)

References 28 publications

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“…Recent studies support the latter as the major mechanism involved in HBV entry [24,25]. Moreover, it has been shown that the machinery involved in the endocytosis of epidermal growth factor receptor (EGFR), which acts as a cofactor for HBV entry, is also involved in the internalization and transport in the endosomal network of HBV [26,27]. The mechanisms leading to HBV escape from endosomes are not yet fully understood, and membrane fusion may be mediated by the fusogenic domains identified in the different surface proteins L, M, and S [7,28].…”

Section: Virus Entrymentioning

confidence: 98%

Early Steps of Hepatitis B Life Cycle: From Capsid Nuclear Import to cccDNA Formation

Dias

Sarica

Neuveut

2021

Viruses

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Hepatitis B virus (HBV) remains a major public health concern, with more than 250 million chronically infected people who are at high risk of developing liver diseases, including cirrhosis and hepatocellular carcinoma. Although antiviral treatments efficiently control virus replication and improve liver function, they cannot cure HBV infection. Viral persistence is due to the maintenance of the viral circular episomal DNA, called covalently closed circular DNA (cccDNA), in the nuclei of infected cells. cccDNA not only resists antiviral therapies, but also escapes innate antiviral surveillance. This viral DNA intermediate plays a central role in HBV replication, as cccDNA is the template for the transcription of all viral RNAs, including pregenomic RNA (pgRNA), which in turn feeds the formation of cccDNA through a step of reverse transcription. The establishment and/or expression of cccDNA is thus a prime target for the eradication of HBV. In this review, we provide an update on the current knowledge on the initial steps of HBV infection, from the nuclear import of the nucleocapsid to the formation of the cccDNA.

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Section: Virus Entrymentioning

confidence: 98%

Early Steps of Hepatitis B Life Cycle: From Capsid Nuclear Import to cccDNA Formation

Dias

Sarica

Neuveut

2021

Viruses

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“…HBV endocytosis is mediated by EGFR, which forms a physical complex with NTCP, by a mechanism requiring EGFR ubiquitination and intrinsic tyrosine kinase activity ( Iwamoto et al., 2019 ). However, rather than requiring downstream signaling molecules such as PI3K or MAPK, HBV relies on the interaction between EGFR and host cell adaptor molecules regulating its intracellular trafficking (e.g., AP2A1, EPS15) for productive infections ( Iwamoto et al., 2019 ; Iwamoto et al., 2020 ). These results suggest that the EGFR endocytic machinery drives the translocation of NTCP-bound HBV from the cell surface through the endosomal network to late endosomes and lysosomes.…”

Section: Viruses Utilizing Egfr For Host Cell Entrymentioning

confidence: 99%

Role of EGF Receptor Regulatory Networks in the Host Response to Viral Infections

Carlin

2022

Front. Cell. Infect. Microbiol.

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In this review article, we will first provide a brief overview of EGF receptor (EGFR) structure and function, and its importance as a therapeutic target in epithelial carcinomas. We will then compare what is currently known about canonical EGFR trafficking pathways that are triggered by ligand binding, versus ligand-independent pathways activated by a variety of intrinsic and environmentally induced cellular stresses. Next, we will review the literature regarding the role of EGFR as a host factor with critical roles facilitating viral cell entry and replication. Here we will focus on pathogens exploiting virus-encoded and endogenous EGFR ligands, as well as EGFR-mediated trafficking and signaling pathways that have been co-opted by wild-type viruses and recombinant gene therapy vectors. We will also provide an overview of a recently discovered pathway regulating non-canonical EGFR trafficking and signaling that may be a common feature of viruses like human adenoviruses which signal through p38-mitogen activated protein kinase. We will conclude by discussing the emerging role of EGFR signaling in innate immunity to viral infections, and how viral evasion mechanisms are contributing to our understanding of fundamental EGFR biology.

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“…Interactions between HBV and NTCP are responsible for the viral endocytosis (Figure 3). According to recent studies, a complex formed between NTCP and the epidermal growth factor receptor (EGFR) contributes to the HBV entry [26]. Due to its complicated structure, NTCP can be oligomerized, and this process seems to affect the viral internalization into the cell.…”

Section: Viral Entrymentioning

confidence: 99%

Recent Advances in Hepatitis B Treatment

et al. 2021

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Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a “functional cure” of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.

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The machinery for endocytosis of epidermal growth factor receptor coordinates the transport of incoming hepatitis B virus to the endosomal network

Cited by 46 publications

References 28 publications

Early Steps of Hepatitis B Life Cycle: From Capsid Nuclear Import to cccDNA Formation

Early Steps of Hepatitis B Life Cycle: From Capsid Nuclear Import to cccDNA Formation

Role of EGF Receptor Regulatory Networks in the Host Response to Viral Infections

Recent Advances in Hepatitis B Treatment

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