Comparative genomics of hepatitis A virus, hepatitis C virus, and hepatitis E virus provides insights into the evolutionary history of Hepatovirus species

Wassenaar, Trudy M.; Jun, Se-Ran; Robeson, Michael; Ussery, David W.

The genome of HAV is approximately 7.5 kb long and encodes a polyprotein that is processed into four structural and six nonstructural proteins by a proteinase (recently reviewed in McKnight & Lemon, 2018) . In lack of the cap assembly that is common in other RNA virus species, translation of HAV is initiated by a secondary structure formed by the 5′-untranscribed region of the RNA genome, which functions as a ribosome entry site (McKnight & Lemon, 2018; Vaughan et al., 2014) . Of note is that the codon use of HAV is quite distinct from that of its host, a property that is also reflected by its low GC content (37%); as a consequence, this virus is slow to replicate in human cells. The virus is transmitted via the fecal-oral route, and the relative high stability of unenveloped virus particles in the environment enables transmission via fecally contaminated food and water. Yearly, approximately 1.5 million clinical cases of HAV occur globally, although at least ten times as many new undocumented infections may occur, as suggested by serological evidence (reviewed in Vaughan et al., 2014 ). The infection is mostly self-limiting and results in lifelong immunity.