Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates Efficient Replication of Genotype-1 Hepatitis E Virus

• DOI: 10.1371/journal.ppat.1005521
• Publication Date: 2016-04-01T13:31:28Z
• Authors: Vidya P. Nair; Saumya Anang; Chandru Subramani; Abhilasha Madhvi; Karishma Bakshi; Akriti Srivastava; Shalimar; Baibaswata Nayak; Ranjith Kumar CT; Milan Surjit
• Keywords: Hepatitis E Virus; Host factors

Hepatitis E virus (HEV) causes acute hepatitis in many parts of the world including Asia, Africa and Latin America. Though self-limiting normal individuals, it results ~30% mortality infected pregnant women. It has also been reported to cause chronic organ transplant patients. Of seven viral genotypes, genotype-1 infects humans is a major public health concern South Asian countries. Sporadic cases genotype-3 4 infection human animals such as pigs, deer, mongeese have primarily from industrialized Genotype-5, 6 7 viruses are known infect wild boar camel, respectively. Genotype-3 successfully propagated laboratory mammalian cell culture. However, replicates poorly culture no other efficient model exists study its life cycle. Here, we report that endoplasmic reticulum (ER) stress promotes HEV replication by inducing cap-independent, internal initiation mediated translation novel protein (named ORF4). Importantly, ORF4 expression stimulatory effect ER inducers on specific genotype-1. sequence mostly conserved among isolates antibodies were detected patient serum. interacted with multiple host proteins assembled complex consisting helicase, RNA dependent polymerase (RdRp), X, eEF1α1 (eukaryotic elongation factor 1 isoform-1) tubulinβ. In association eEF1α1, stimulated RdRp activity. Furthermore, hepatoma cells stably express or engineered proteasome resistant mutant genome permitted enhanced replication. These findings reveal positive role promoting pave way towards development an virus.