Research Topic

Origin and Evolution of Hepatitis Viruses

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Infection with Hepatitis A, B, C, D and E viruses results in the syndrome of hepatitis, characterized by inflammation of the liver, resulting in 1.4 million deaths per year. Although each virus is classified within a completely different virus family, they all have hepatocyte-specific tropism and similar ...

Infection with Hepatitis A, B, C, D and E viruses results in the syndrome of hepatitis, characterized by inflammation of the liver, resulting in 1.4 million deaths per year. Although each virus is classified within a completely different virus family, they all have hepatocyte-specific tropism and similar clinical manifestations. Infection with hepatitis viruses other than hepatitis A may result in persistent, chronic infection with varying degrees of risk. However, the route of transmission varies among the hepatitis viruses, including faecal-oral transmission (HAV and HEV) and bloodborne/parenteral transmission (HBV, HCV, HDV). Full permissive infection with human hepatitis viruses is limited to higher primates, except for HEV, yet hepatitis-like viruses are known to infect all manner of vertebrates, including placental mammals of the Laurasiatheria clade, such as bats and other insectivorous small mammals, suggesting an ancient origin for the hepatitis viruses with complex evolutionary histories. The definitive origin of the hepatitis viruses remains largely unknown.

Interesting similarities exist among hepatitis viruses, suggesting possible shared evolutionary elements which would be interesting to explore. For example, HAV and HEV share the feature of host lipid envelopment during the systemic phase yet are shed as naked particles. Although their genomes are highly divergent, both HEV and HCV share highly similar codon usage, including nucleotide and amino acid composition. HBV endogenous elements have been found in bird, reptile and insect genomes, suggesting a complex and ancient evolutionary history. Similarly, it has been speculated that primordial evolution of HAV may involve a picorna-like insect virus, as evidenced by codon usage, amino acid composition and capsid similarities. HDV is considered to be a subviral satellite of HBV due to the requirement for HBsAg during virion assembly, release and receptor binding, yet recent evidence has shown that glycoproteins of HBV-unrelated viruses, including HCV, can support HDV replication in vitro. Interestingly, both HBV and HDV share some similarities with plant viruses; for example, the HBV genome structure and mode of replication shares a distinct resemblance with the Caulimovirus plant virus family and HDV shares genome organization and replicative features with plant viroids and virusoids. Furthermore, all hepatitis virus genotypes infecting humans show distinct global geographic distribution, further suggesting association with original peoples and historical migration patterns.

This research topic will provide a platform for discourse regarding the historical evolution and origin of the five hepatitis viruses, HAV to HEV. Understanding the course of human hepatitis virus evolution helps inform our understanding of the current molecular epidemiology and clinical impact of these viruses. The intriguing similarities among the evolutionary history of different hepatitis viruses is an interesting theme to be explored. Exploration of gaps in our understanding of viral hepatitis evolutionary history are also encouraged and may include:

• The vast differential in genetic diversity among the hepatitis viruses, ranging from the relatively static and slow evolutionary rate of hepatitis A virus to the rapid and extraordinarily extensive level of genetic diversity of HCV

• The impacts of ancestral host shifts, host co-evolution and extinct lineages on the course of viral hepatitis evolution, particularly the role of insect-like viruses, genomic elements and the interesting lack of a primate HCV-like virus

• The influence of recombination (within intra- and inter-species hosts) on the course of hepatitis virus evolution

• The zoonotic origin or potential of hepatitis viruses (including with respect to climate change and host habitat pressures)

This Topic will accept the following manuscript types: Hypothesis and Theory, Methods, Original Research, Mini Reviews and Perspectives.

Topic Image Details:

3D renderings of the Cryo-EM structure for the HAV full particle (PDB ID 5WTE), the HBV T=4 capsid strain adyw complexed with assembly effector HapI (PDB ID 2G34), the HCV polymerase NS5B (Con1 1-570) with HCV-796 inhibitor (PDB ID 3FQL), the HDV antigen oligomerization domain (PDB ID 1A92), and the HEV-like particle crystal structure (PDB ID 3HAG) were obtained from the National Centre for Biotechnology Information (NCBI) Structure Molecular Modeling Database (MMDB): Madej T, Lanczycki CJ, Zhang D, Thiessen PA, Geer RC, Marchler-Bauer A, Bryant SH. MMDB and VAST+: tracking structural similarities between macromolecular complexes. Nucleic Acids Res. 2014 Jan 1;42(1):D297-303. Epub 2013 Dec 6. doi: 10.1093/nar/gkt1208. [PubMed PMID: 24319143]

The Hepadnaviridae (HBV) phylogenetic tree was prepared by Remco Bouckaert and Julian Tang. Animal pictures at the tree tips signify HBV sequences from species included in the analysis. Letters denote human HBV genotypes and a human skull denotes ancient HBV DNA sequence.


Keywords: phylogeny, geographic distribution, recombination, host shift, species tropism, most recent common ancestor


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