Replication of the HEV genome:- ü HEV replicates in the hepatocytes and is excreted in stool ü A general model of HEV replication has been proposed, based on similarities and sequence homology to other more completely characterized +RNA viruses. ü As HEV enters into a permissive cell, the viral genomic RNA is translated in the cytosol of infected cells to produce the nonstructural ORF1-encoded polyprotein (nsP). ü Because it contains the viral replicase, nsP is postulated to replicate the genomic positive strand into the negative strand replicative intermediate. ü This intermediate, in analogy with alphaviruses, is postulated to act as a template for the synthesis of additional copies of the genomic positive strand as well as a subgenomic positive strand. ü The analogy to alphavirus replication is presumed because of the presence in HEV negative-strand RNA of a sequence stretch that is similar to the junction sequence found in the RNA replicative intermediate of the Sindbis alphavirus. ü During alphavirus RNA replication, this junction sequence acts as a subgenomic promoter for transcription of the structural region mRNA. ü The proposed subgenomic positive-strand HEV RNA can then be translated into the structural protein(s) at late stages of viral replication. ü The structural (capsid) protein then probably packages the viral genome to form progeny virions. ü However, direct experimental confirmation of this replication scheme is still awaited.