The unexpected structures of hepatitis C virus envelope proteins

Wang, Yunyun; Wang, Jing; Wu, Shanshan; Zhu, Haihong

doi:10.3892/etm.2017.4745

Cited by 4 publications

(5 citation statements)

References 67 publications

(105 reference statements)

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“…The core of E2 has been solved in complex with antibodies [28–30], where E2 adopts a central immunoglobin-like fold formed by β-sheets surrounded by short α-helices dispersed in loops. However, both E1 and E2 used for structural studies are truncated proteins, part of the ectodomains are missing in the solved structures [31, 32]. Meanwhile, several groups have been trying to co-express E1E2 heterodimer to ensure the correct folding of the intact proteins as the folding and maturation of E1 and E2 may depend on each other [33–36].…”

Section: Introductionmentioning

confidence: 99%

Functional expression and characterization of the envelope glycoprotein E1E2 heterodimer of hepatitis C virus

Cao

Kong

et al. 2019

PLoS Pathog

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Hepatitis C virus (HCV) is a member of Hepacivirus and belongs to the family of Flaviviridae . HCV infects millions of people worldwide and may lead to cirrhosis and hepatocellular carcinoma. HCV envelope proteins, E1 and E2, play critical roles in viral cell entry and act as major epitopes for neutralizing antibodies. However, unlike other known flaviviruses, it has been challenging to study HCV envelope proteins E1E2 in the past decades as the in vitro expressed E1E2 heterodimers are usually of poor quality, making the structural and functional characterization difficult. Here we express the ectodomains of HCV E1E2 heterodimer with either an Fc-tag or a de novo designed heterodimeric tag and are able to isolate soluble E1E2 heterodimer suitable for functional and structural studies. Then we characterize the E1E2 heterodimer by electron microscopy and model the structure by the coevolution based modeling strategy with Rosetta, revealing the potential interactions between E1 and E2. Moreover, the E1E2 heterodimer is applied to examine the interactions with the known HCV receptors, neutralizing antibodies as well as the inhibition of HCV infection, confirming the functionality of the E1E2 heterodimer and the binding profiles of E1E2 with the cellular receptors. Therefore, the expressed E1E2 heterodimer would be a valuable target for both viral studies and vaccination against HCV.

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Section: Introductionmentioning

confidence: 99%

Functional expression and characterization of the envelope glycoprotein E1E2 heterodimer of hepatitis C virus

Cao

Kong

et al. 2019

PLoS Pathog

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“…HCV is a single stranded RNA virus whose genome has single open reading frame (ORF) 9600 bp long ( Table 1 ) [ 37 ]. The N -terminal part of the ORF encodes structural proteins including core and envelope glycoproteins, whereas the remaining part of the ORF encodes for the nonstructural proteins [ 40 ].…”

Section: Hepatitis C Virusmentioning

confidence: 99%

“…Also, most HPV infections in newborns are transmitted vertically from the mother during pregnancy, delivery, or later, by saliva [15]. − Linear double stranded DNA [36] Single stranded RNA [37] Double stranded circular DNA [38,39] Genome Approximately 8 kb in size [16] − Approximately 180 kb in size [36] 9 600 bp in size [37,40] The smallest genome with 3200 bp in size [38]…”

Section: Hpv Genome and Mechanism Of Infectionmentioning

confidence: 99%

“…Kerationocytes and mucosal sufraces [16] − B-cells and epithelial cells [10,41] Hepatocytes, lymphocytes, and salivary gland cells [42] Hepatocytes and lymphocytes [43] Major viral oncoproteins E6, E7 [15,16,24] − LMP1, LMP2A, EBNA1 [10,44] NS3 or NS5A [40,42,45] S, C, P and X [39,46] Virus transmission mode Sexual contact, self-inoculation, vertical and horizontal transmissions [47] − Sexual contact, blood or saliva transmission [10] Vertical transmission, horizontal transmission (sex or sharing of drug-injection needles) [39] Sexual contact, self-inoculation, vertical and horizontal transmissions [47]…”

Section: Tropismmentioning

confidence: 99%

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Meet the Insidious Players: Review of Viral Infections in Head and Neck Cancer Etiology with an Update on Clinical Trials

2021

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Head and neck cancers (HNC) occur in the upper aerodigestive tract and are among the most common cancers. The etiology of HNC is complex, involving many factors, including excessive tobacco and alcohol consumption; over the last two decades, oncogenic viruses have also been recognized as an important cause of HNC. Major etiological agents of nasopharynx carcinoma and oropharyngeal carcinoma include Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), both of which are able to interfere with cell cycle control. Additionally, the association of hepatitis C and hepatitis B infection was observed in oral cavity, oropharyngeal, laryngeal, and nasopharyngeal cancers. Overall prognoses depend on anatomic site, stage, and viral status. Current treatment options, including radiotherapy, chemotherapy, targeted therapies and immunotherapies, are distributed in order to improve overall patient prognosis and survival rates. However, the interplay between viral genome sequences and the health, disease, geography, and ethnicity of the host are crucial for understanding the role of viruses and for development of potential personalized treatment and prevention strategies. This review provides the most comprehensive analysis to date of a vast field, including HNC risk factors, as well as viral mechanisms of infection and their role in HNC development. Additionally, currently available treatment options investigated through clinical practice are emphasized in the paper.

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“…It is a viral infection characterized by the inflammation of liver parenchyma [7]. Hepatitis C Virus is a single-stranded enveloped RNA virus belongs to the genus Hepacivirus of Flaviviruses [8]. Seven different genotypes (1-7) have been isolated which are identifiable on the basis of their nucleotide sequence [9].…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Electrochemiluminescence Assay and Chemiluminescent Microparticle Immunoassay for the Screening of Hepatitis C

Wadood

Usman

2018

Indian J Hematol Blood Transfus

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The primary objective of the study was to identify a highly sensitive and specific screening technique for the detection of Hepatitis C infection in healthy blood donors in a low prevalence area for HCV. In this study, two of the most commonly used methods for Anti-HCV screening, i.e., Electrochemiluminescence Immunoassay (ECLIA) and Chemiluminescent Microparticle Immunoassay (CMIA) were performed among 517 selected healthy blood donors. The clinical performance of ECLIA and CMIA was compared on the basis of their operational variables, i.e., Sensitivity, Specificity, Accuracy, Youden's J index, Positive and Negative predictive values and False discovery, False positive and False negative rate, etc., Both ECLIA and CMIA are highly sensitive (100%) and specific (98%) in terms of anti HCV detection among the blood donors. According to the clinical performance of ECLIA and CMIA, both are efficient in detecting anti-HCV antibodies among the asymptomatic population of healthy blood donors. But as both of them are associated with false positive results, it is recommended to have Polymerase chain reaction on the reactive samples to detect the HCV RNA.

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The unexpected structures of hepatitis C virus envelope proteins

Cited by 4 publications

References 67 publications

Functional expression and characterization of the envelope glycoprotein E1E2 heterodimer of hepatitis C virus

Functional expression and characterization of the envelope glycoprotein E1E2 heterodimer of hepatitis C virus

Meet the Insidious Players: Review of Viral Infections in Head and Neck Cancer Etiology with an Update on Clinical Trials

Comparative Analysis of Electrochemiluminescence Assay and Chemiluminescent Microparticle Immunoassay for the Screening of Hepatitis C

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