Hepatitis E virus (HEV) open reading frame 2: Role in pathogenesis and diagnosis in HEV infections

Sayed, Ibrahim M.; Ramadan, Haidi Karam‐Allah; Hafez, Mahmoud H. R.; Elkhawaga, Amal A.; El‐Mokhtar, Mohamed A.

doi:10.1002/rmv.2401

Cited by 6 publications

(2 citation statements)

References 149 publications

(392 reference statements)

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“…Several other reports showed that HEV is excreted in the urine of HEV-3 and/or HEV-4-infected patients or non-human primates with evidence of kidney injury [ 24 , 39 ]. The replication of HEV in the kidney was confirmed by the detection of negative-strand HEV RNA, HEV ORF2 antigen, and other histopathological changes in known animal models such as pigs, non-human primates, rabbits, and Mongolian gerbils [ 24 , 26 , 40 , 41 , 42 ]. HEV is released in the urine, and the urine of HEV-infected monkeys was found to contain viral particles that were infectious to naïve monkeys [ 24 ].…”

Section: Discussionmentioning

confidence: 97%

First Report on Abnormal Renal Function in Acute Hepatitis E Genotype 1 Infection

et al. 2023

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Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients’ age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections.

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Section: Discussionmentioning

confidence: 97%

First Report on Abnormal Renal Function in Acute Hepatitis E Genotype 1 Infection

et al. 2023

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“…Anemia was the most common observed side effect in first-line ribavirin therapy. Pegylated interferon-α has also been used successfully for HEV treatment but is associated with many adverse effects including cholestasis and teratogenicity [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

et al. 2023

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Hepatitis E virus (HEV) is the notable causative agent of acute and chronic hepatic, renal, pancreatic, neurological, and hematopoietic blood cell infections with high risk in immunocompromised patients. Hepatic failure is mostly documented among adults, pregnant women, and patients with preexisting liver disease. HEV is a positive sense RNA virus of 7.2 kb genome size with typically three open reading frames (ORFs) which play essential roles in viral replication, genome assembly, and transcription. The mutational substitution in the viral RNA genome makes more it difficult to understand the actual relationship in the host–virus association. ORFs of HEV encode different structural and non-structural proteins and one of them is the capsid protein which is coded by ORF2. The capsid protein mediates the encapsulation of the viral genome as well as being involved in virion assembly. In the current study, the ligand-based docking approach was employed to inhibit the active amino acids of the viral capsid protein. Depending upon S-score, ADMET profiling, and drug scanning, the top ten tetrapeptides were selected as potential drug candidates with no toxicity counter to HEV receptor protein. The S-score or docking score is a mathematical function which predicts the binding affinities of docked complexes. The binding affinity of the predicted drug–target complexes helps in the selectivity of the desired compound as a potential drug. The best two selected peptides (i.e., TDGH with S-score of −8.5 and EGDE with S-score of −8.0) interacted with the active site amino acids of the capsid protein (i.e., Arg399, Gln420, and Asp444). The molecular dynamics simulations of RMSD trajectories of TDGH–capsid protein and EDGE–capsid protein have revealed that both docked complexes were structurally stable. The study revealed that these tetrapeptides would serve as strong potential inhibitors and a starting point for the development of new drug molecules against the HEV capsid protein. In future, in vivo studies are needed to explore selected peptides as potential drug candidates.

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Recent advances in electrochemical aptasensors and genosensors for the detection of pathogens

Nazari-Vanani,

Negahdary

2024

Environmental Research

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Hepatitis E virus (HEV) open reading frame 2: Role in pathogenesis and diagnosis in HEV infections

Cited by 6 publications

References 149 publications

First Report on Abnormal Renal Function in Acute Hepatitis E Genotype 1 Infection

First Report on Abnormal Renal Function in Acute Hepatitis E Genotype 1 Infection

Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

Recent advances in electrochemical aptasensors and genosensors for the detection of pathogens

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