Hepatitis Virus
Hepatitis Viruses | Genome Organization and Encoded Proteins | eEnzyme
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About Hepatitis Viruses
Viral hepatitis is caused principally by five biologically unrelated human pathogens: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). They share a primary association with liver inflammation but differ substantially in taxonomy, virion architecture, genome type, transmission route, replication strategy, and capacity to establish chronic infection.
HAV is a small positive-sense RNA virus in the family Picornaviridae. HEV is a positive-sense RNA virus in the family Hepeviridae. Both are transmitted mainly by the fecal–oral route and most often cause acute, self-limited hepatitis, although chronic HEV infection can occur in immunocompromised individuals.
HBV is an enveloped reverse-transcribing DNA virus in the family Hepadnaviridae. Its compact, partially double-stranded circular DNA genome is converted in the nucleus into covalently closed circular DNA, which serves as the persistent transcriptional template for viral RNAs. HBV infection may be acute or chronic and can lead to cirrhosis and hepatocellular carcinoma.
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Overview of the five principal human hepatitis viruses.
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HCV is an enveloped positive-sense RNA virus in the family Flaviviridae and genus Hepacivirus. Its genome is translated as a single polyprotein that is processed into structural and nonstructural proteins. HCV frequently establishes persistent infection and, without treatment, may progress over years to advanced liver disease.
HDV is a small satellite virus in the family Kolmioviridae and genus Deltavirus. It contains a circular, negative-sense single-stranded RNA genome and encodes delta antigen. HDV depends on HBV surface proteins to assemble and release infectious particles; therefore, human HDV infection occurs only in association with HBV coinfection or superinfection.
The five hepatitis viruses therefore do not share a common genome organization or conserved protein set. A comparative format is the most accurate way to describe their biology. Their viral proteins are widely studied in relation to entry, replication, immune responses, persistence, diagnostics, vaccines, and antiviral drug development.
Genome Organization & Encoded Proteins
HAV, HBV, HCV, HDV, and HEV use distinct genome organizations and expression strategies. HAV, HCV, and HEV contain positive-sense RNA genomes; HBV contains a relaxed circular, partially double-stranded DNA genome and replicates through an RNA intermediate; and HDV contains a small circular negative-sense RNA genome. The following tables summarize their principal genomic and protein features.
| Virus |
Taxonomy |
Genome |
Virion Form |
Expression / Replication Strategy |
| HAV |
Picornaviridae
Hepatovirus |
Positive-sense ssRNA, approximately 7.5 kb |
Non-enveloped in feces; quasi-enveloped in blood |
One polyprotein processed into capsid and nonstructural proteins |
| HBV |
Hepadnaviridae
Orthohepadnavirus |
Relaxed circular, partially dsDNA, approximately 3.2 kb |
Enveloped |
Nuclear cccDNA transcription followed by reverse transcription of pregenomic RNA |
| HCV |
Flaviviridae
Hepacivirus |
Positive-sense ssRNA, approximately 9.6 kb |
Enveloped |
One polyprotein processed into structural and nonstructural proteins |
| HDV |
Kolmioviridae
Deltavirus |
Circular negative-sense ssRNA, approximately 1.7 kb |
Enveloped with HBV-derived surface proteins |
Host-polymerase-dependent rolling-circle replication; requires HBV for infectious particle formation |
| HEV |
Hepeviridae
Paslahepevirus |
Positive-sense ssRNA, approximately 7.2 kb |
Non-enveloped in feces; quasi-enveloped in blood |
ORF1 replication polyprotein plus subgenomic expression of ORF2 and ORF3 |
| Virus |
Protein or Protein Group |
Principal Function |
| HAV |
VP1–VP4 |
Form the capsid, protect the RNA genome, and contribute to attachment, entry, antigenicity, and particle stability. |
| 3C Protease |
Processes the viral polyprotein at multiple cleavage sites. |
| 3D Polymerase |
RNA-dependent RNA polymerase responsible for viral genome replication. |
| HBV |
Surface Proteins — L, M, and S |
Form the viral envelope; mediate attachment and entry; constitute hepatitis B surface antigen (HBsAg). |
| Core Protein — HBcAg |
Forms the nucleocapsid and packages pregenomic RNA together with polymerase. |
| Precore / HBeAg |
Produces secreted hepatitis B e antigen and contributes to immune regulation and clinical assessment of infection. |
| Polymerase |
Contains terminal-protein, reverse-transcriptase, and RNase H activities required for genome replication. |
| HBx |
Regulatory protein that supports cccDNA transcription and alters host signaling, transcription, and protein-degradation pathways. |
| HCV |
Core |
Forms the nucleocapsid and participates in viral assembly and host-cell interactions. |
| E1 and E2 |
Envelope glycoproteins involved in receptor interactions, entry, membrane fusion, and antibody recognition. |
| NS3/4A |
Protease-helicase complex required for polyprotein processing and RNA replication. |
| NS5A |
Multifunctional phosphoprotein involved in replication-complex organization, assembly, and host interactions. |
| NS5B |
RNA-dependent RNA polymerase that synthesizes the viral RNA genome. |
| HDV |
Small Delta Antigen |
Required for HDV RNA replication and ribonucleoprotein formation. |
| Large Delta Antigen |
Suppresses replication at later stages and promotes particle assembly through interaction with HBV surface proteins. |
| HEV |
ORF1 Polyprotein |
Contains functional domains involved in RNA capping, helicase activity, and RNA-dependent RNA polymerase activity. |
| ORF2 Capsid Protein |
Forms the capsid and is a major target of the humoral immune response. |
| ORF3 Protein |
Small multifunctional protein involved in particle release and interactions with host-cell pathways. |
Scientific Resources & Further Reading
The following trusted organizations and databases provide current information on hepatitis-virus taxonomy, genome organization, transmission, prevention, disease, viral sequences, and protein structures.
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