Type A viral hepatitis: A summary and update on the molecular virology, epidemiology, pathogenesis and prevention  Stanley M. Lemon, Jördis J. Ott, Pierre Van Damme, Daniel Shouval  Journal of Hepatology  Volume 68, Issue 1, Pages 167-184 (January 2018) DOI: 10.1016/j.jhep.2017.08.034 Copyright © 2017 European Association for the Study of the Liver Terms and Conditions

Fig. 1 (Top) Organisation of the ∼7.5kb HAV genome. The ORF is shown as a box, flanked by the 5′ and 3′ UTRs. The 5′UTR is covalently linked to a small viral protein, VPg (or 3B), the protein primer for RNA synthes is at its 5′ end, and contains an IRES that directs translation of the downstream ORF. The 3′UTR terminates in a 3′ poly(A) tail. Individual viral proteins are processed from the polyprotein as described in the text. Except for the VP0 (VP4-VP2) maturation cleavage and VP1-pX cleavage, all are mediated by 3Cpro, a cysteine protease and the only protease expressed by the virus. (Bottom) Transmission electron micrographs of eHAV and naked HAV particles found in the supernatant media of infected cell cultures (Reproduced with permission from Feng et al.)16 eHAV, quasi-enveloped hepatitis A virus; ORF, open reading frame. Journal of Hepatology 2018 68, 167-184DOI: (10.1016/j.jhep.2017.08.034) Copyright © 2017 European Association for the Study of the Liver Terms and Conditions

Fig. 2 eHAV biogenesis. Assembled HAV capsids are recruited to ESCRT by interactions of the VP2 capsid protein with ALIX (PDCD6IP), and bud into late endosomes to form MVBs. Fusion of the limiting membrane of the MVB with the plasma membrane releases quasi-enveloped eHAV virions to the extracellular space. eHAV, quasi-enveloped hepatitis A virus; ESCRT, endosomal sorting complexes required for transport; ILV, intralumenal vesicle; MVB, multivesicular bodies. Journal of Hepatology 2018 68, 167-184DOI: (10.1016/j.jhep.2017.08.034) Copyright © 2017 European Association for the Study of the Liver Terms and Conditions

Fig. 3 HAV pathogenesis in an experimentally infected chimpanzee. Showing from the top: early but weak type 1 interferon and ISG responses associated with the transient appearance of pDCs in the liver; peripheral blood CD8+ and CD4+ T cell responses determined by intracellular cytokine staining when stimulated with HAV peptides, and CD8+ T cell frequencies determined by staining with three tetramers; IgM and IgG antibody responses determined by ELISA; and, viral RNA genome equivalents detected in serum, faeces, and liver. Reproduced with permission from.70 ALT, alanine aminotransferase; HAV, hepatitis A virus; ISG, interferon-stimulated gene; pDCs, plasmacytoid dendritic cells. Journal of Hepatology 2018 68, 167-184DOI: (10.1016/j.jhep.2017.08.034) Copyright © 2017 European Association for the Study of the Liver Terms and Conditions

Fig. 4 Estimated prevalence of hepatitis A virus, 2005. Reproduced with permission from.77 Journal of Hepatology 2018 68, 167-184DOI: (10.1016/j.jhep.2017.08.034) Copyright © 2017 European Association for the Study of the Liver Terms and Conditions

Fig. 5 Age distribution of reported deaths from (n = 689, upper panel) and reported cases of (n = 235 153, lower panel) hepatitis A within the US, 1983–1991 (2). Bars represent reported deaths or cases (left ordinate), lines represent incidence rates (right ordinate). Reprinted with permission from.90 Journal of Hepatology 2018 68, 167-184DOI: (10.1016/j.jhep.2017.08.034) Copyright © 2017 European Association for the Study of the Liver Terms and Conditions

Fig. 6 HAV genotype classification. Phylogenetic analysis of the six currently recognised HAV genotypes. Reproduced with permission from.72 HAV, hepatitis A virus. Journal of Hepatology 2018 68, 167-184DOI: (10.1016/j.jhep.2017.08.034) Copyright © 2017 European Association for the Study of the Liver Terms and Conditions

Fig. 7 Incidence of acute hepatitis A in Israel between January 1992 and December 2016. UMV was started in 1999 with administration of an inactivated HAV vaccine at 18 and 24 months of age. Data collected through passive surveillance of the Israeli Ministry of Health (MOH). (Received by curtesy of Dr E. Anis, MOH, Israel). HAV, hepatitis A virus; UMV, universal mass vaccination. Journal of Hepatology 2018 68, 167-184DOI: (10.1016/j.jhep.2017.08.034) Copyright © 2017 European Association for the Study of the Liver Terms and Conditions

Fig. 8 Impact of the single-dose immunisation strategy against hepatitis A in Argentina. (Reproduced with permission from177). Journal of Hepatology 2018 68, 167-184DOI: (10.1016/j.jhep.2017.08.034) Copyright © 2017 European Association for the Study of the Liver Terms and Conditions