https://www.selleckchem.com/products/dorsomorphin-2hcl.html Coordinated assembly of viral and host factors is essential for the successful propagation of viruses as well as the generation of host anti-viral response. Previous studies from our group, as well as from other groups, have identified host proteins interacting with various components of the Hepatitis E virus (HEV). However, the functional relevance of host protein interactions in HEV replication context has been notably overlooked. The present study reports that heterogeneous nuclear ribonucleoproteins (hnRNPs), namely hnRNPK, hnRNPA2B1, hnRNPH, PCBP1, and PCBP2 interact with HEV RNA promoter and RNA dependent RNA polymerase to regulate HEV replication. We found that hnRNPK and hnRNPA2B1 are the virus supportive factors interacting with HEV RNA at promoter regions along with HEV polymerase protein, which are essential for HEV replication in the cells. Contrarily, hnRNPH, PCBP1, and PCBP2 are the anti-viral factors that interact exclusively with HEV genomic promoter and inhibit HEV replication in Huh7 S10-3 cells. In-vitro RNA binding assays revealed that the anti-viral hnRNP proteins hamper the binding of virus supportive hnRNP proteins at HEV genomic promoter. In the binding reaction, the binding of HEV polymerase protein to the genomic promoter is slightly affected by the presence of anti-viral hnRNPH. In an effort of visualizing the subcellular localization of hnRNP proteins in the HEV replication scenario in the Huh7 cells, we showed that hnRNPK, hnRNPA2B1, hnRNPH, PCBP1, and PCBP2 redistribute from nucleus to cytoplasm. In conclusion, our study highlights the importance of hnRNP proteins in HEV replication regulation. Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) constitute aggressive neurodegenerative pathologies that lead to the progressive degeneration of upper and lower motor neurons and of neocortical areas respectively. In the past decade, the identification of several ge