Open Reading Frame 4 - A Multifunctional Protein of Hepatitis E Virus

Hepatitis E virus (HEV) is the most frequent cause of acute viral hepatitis across the globe. Historically, the lack of an efficient in vitro culture system has significantly hampered hepatitis E virus (HEV) research. Although the disease was discovered in the late 1980s, the precise molecular mechanisms underlying the higher pregnancy mortality associated with HEV remain elusive. This gap in understanding is largely due to the challenges in virus propagation in cell cultures and the inability of genotype 3 HEV to replicate pregnancy-related mortality in pig models. Recently, there have been advancements with various research groups successfully propagating different HEV strains in non-hepatic cell lines. However, an efficient and highly propagating in vitro system for genotype 1 strains in human liver cells remains unavailable. The absence of an efficient culture system and a genotype 1 animal pregnancy model is a significant barrier to understanding the mechanisms behind HEV-induced pregnancy mortality.

The HEV genome is a single-stranded, positive-sense RNA molecule of about 15 kb and systematized into three open reading frames (ORFs), encoding both structural and non-structural proteins. HEV GT 1 is known to encode an additional open reading frame (ORF4), which is expressed only during endoplasmic reticulum (ER) stress. ORF4 is believed to play a crucial functional role in the viral replication cycle of GT 1 of HEV. In this book, we will focus on ORF4 protein genes, reviewing recent research progresses, that provide insights into HEV biology.

This book provides insights into significant aspects of less understood ORF4 including, physicochemical parameters, amino acid distribution patterns, genetic variability features, mutational and entropy analyses, disorder phenomenon and structural analyses. The first chapter gives a brief introduction to HEV genome, structural and non-structural proteins and replication. The second and third chapters deal with physicochemical aspects and amino acid composition patterns of ORF4. Next chapter describes the mutation, entropy and selection pressure analyses in ORF4. The final chapter deals with the potential of ORF4 structure and its role as a potential drug molecule, thus can accelerate the process of drug designing strategies against HEV.

The present book aims to provide fundamental knowledge and noteworthy information on various bioinformatics predictor tools to students, researchers, academicians, and the general public. Although significant progress has been made in understanding the role of ORF4 in the biology of the Hepatitis E virus, further studies are needed worldwide to deepen this understanding.

I would like to thank my Husband and Family. Without their support, this book would not have been published. Finally, I sincerely hope this book provides useful information and will be of benefit to all its readers.