Hepatitis E virus (HEV) is the leading cause of enterically transmitted viral hepatitis globally, and is responsible for 20 million infections and 70,000 deaths every year. Though HEV infection is usually self-resolving, severe forms or chronic infections have been described, mainly in immunocompromised patients. A high rate of mortality has also been reported among pregnant women. The diagnosis of hepatitis E is based on the detection of anti-HEV antibodies and/or viral RNA in patient serum. rnHEV is a quasi-enveloped, positive-sense RNA virus expressing three open reading frames (ORFs). In particular, ORF2 encodes the ORF2 viral capsid protein, which is involved in particle assembly, binding to host cells and eliciting neutralizing antibodies. Although HEV is a non-enveloped virus in bile and feces, patient serum and cell culture-produced particles have been described to be associated with cellular lipids, as for Hepatitis A virus.rnThe growth of HEV in cell culture has been proven to be very difficult. Notably, the exact sequence of infectious particle-associated ORF2 protein is unknown. In addition, the ultrastructure of particles has never been robustly studied by immune electron microscopy.rnrnThe inventors have now identified the precise sequence of infectious particle-associated ORF2 capsid protein. Strikingly, their analyses revealed that in infected patients, HEV produces three forms of the ORF2 capsid protein: ORF2i, ORF2g and ORF2c. The ORF2i protein is associated with infectious particles whereas ORF2g and ORF2c proteins are massively produced glycoproteins that are not associated with infectious particles and are the major antigens present in HEV-infected patient sera. Accordingly, the ORF2i protein is thus the subject matter of the present invention as well as antibodies specific for the protein and diagnostic assays (e.g. ELISA) for the diagnosis of Hepatitis E virus infection.rnrnScientific publication(s):rnGastroenterology, 2017 Sep 25, Montpellier C. et al., Hepatitis E Virus Lifecycle and Identification of 3 Forms of the ORF2 Capsid Protein, doi: 10.1053/j.gastro.2017.09.020