Role of Envelopment in the HEV Life Cycle

Yin, Xin; Li, Xinlei; Feng, Zongdi

doi:10.3390/v8080229

Cited by 68 publications

(66 citation statements)

References 52 publications

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“…Consistent with this, MAVS abundance is not altered in cells transfected with replication-competent HEV RNAs (Fig. 4B, bottom), although the response to RIG-I and MDA5 agonists is reduced in such cells (Nan et al 2014b;Yin et al 2016). The underlying mechanism is uncertain, but overexpression of the papain-like cysteine protease (PCP) domain of the HEV open reading frame (ORF)1 protein has been shown to result in deubiquitination of RIG-I and TBK1, thereby blocking RIG-I signaling (Nan et al 2014b).…”

Section: Innate Immunity To Enteric Hepatitis Virusessupporting

confidence: 75%

Innate Immunity to Enteric Hepatitis Viruses

Feng

Lemon

2018

Cold Spring Harb Perspect Med

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Although hepatitis A virus (HAV) and hepatitis E virus (HEV) are both positive-strand RNA viruses that replicate in the cytoplasm of hepatocytes, there are important differences in the ways they induce and counteract host innate immune responses. HAV is remarkably stealthy because of its ability to evade and disrupt innate signaling pathways that lead to interferon production. In contrast, HEV does not block interferon production. Instead, it persists in the presence of an interferon response. These differences may provide insight into HEV persistence in immunocompromised patients, an emerging health problem in developed countries.

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Section: Innate Immunity To Enteric Hepatitis Virusessupporting

confidence: 75%

Innate Immunity to Enteric Hepatitis Viruses

Feng

Lemon

2018

Cold Spring Harb Perspect Med

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“…HAV and presumably other nonenveloped viruses, such as HEV, hijack intracellular membranes to shield from neutralizing antibody epitopes contained in the viral capsid. Quasienvelopment is also thought to promote HAV spread within the liver but is mechanistically incompletely understood (39). For HAV, it was demonstrated that the biogenesis of the membranes surrounding virions is dependent on host proteins associated with the ESCRT pathway, specifically VPS4B and ALIX (38).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles

Ding

Heller

Capuccino

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

183

185

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ORF3 86-88A mutant was duplicated and also shown as ORF3 95-97A mutant. In the corrected version of Fig. 5A shown below, we have replaced the duplicate image with the correct original data. After careful reexamination of the original data, we are confident that the error in assembling this figure does not affect the validity of the research or the conclusions that we have drawn. We are grateful to the careful reader who brought this mistake to our attention and apologize for any confusion that this error may have caused." The corrected Fig. 5 and its legend appear below.

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“…ORF1 is a polyprotein required for HEV RNA replication. ORF2 is the capsid protein, while ORF3 is a small protein involved in HEV egress (14). HEV has a unique dual life cycle: it is shed into the feces as naked virions, but circulates in the blood as "quasi-enveloped" particles (eHEV) (15).…”

mentioning

confidence: 99%

Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection

Yin

Dong

Lhomme

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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143

218

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The enterically transmitted hepatitis E virus (HEV) adopts a unique strategy to exit cells by cloaking its capsid (encoded by the viral ORF2 gene) and circulating in the blood as "quasi-enveloped" particles. However, recent evidence suggests that the majority of the ORF2 protein present in the patient serum and supernatants of HEV-infected cell culture exists in a free form and is not associated with virus particles. The origin and biological functions of this secreted form of ORF2 (ORF2) are unknown. Here we show that production of ORF2 results from translation initiated at the previously presumed AUG start codon for the capsid protein, whereas translation of the actual capsid protein (ORF2) is initiated at a previously unrecognized internal AUG codon (15 codons downstream of the first AUG). The addition of 15 amino acids to the N terminus of the capsid protein creates a signal sequence that drives ORF2 secretion via the secretory pathway. Unlike ORF2, ORF2 is glycosylated and exists as a dimer. Nonetheless, ORF2 exhibits substantial antigenic overlap with the capsid, but the epitopes predicted to bind the putative cell receptor are lost. Consistent with this, ORF2 does not block HEV cell entry but inhibits antibody-mediated neutralization. These results reveal a previously unrecognized aspect in HEV biology and shed new light on the immune evasion mechanisms and pathogenesis of this virus.

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Role of Envelopment in the HEV Life Cycle

Cited by 68 publications

References 52 publications

Innate Immunity to Enteric Hepatitis Viruses

Innate Immunity to Enteric Hepatitis Viruses

Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles

Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection

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