Related Experiment Video
Updated: May 8, 2026
13:04
A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
Evolutionary analysis of hepatitis C virus gene sequences from 1953
Rebecca R Gray1, Yasuhito Tanaka, Yutaka Takebe
1Department of Zoology, University of Oxford, , Oxford, UK.
Summary
Two 1953 hepatitis C virus (HCV) sequences provide the oldest genetic evidence of HCV infection. Evolutionary analysis using these historical viral sequences refines estimates of the virus
Area of Science:
- Virology and Evolutionary Biology
- Infectious Disease Epidemiology
- Phylogenetics and Molecular Evolution
Background:
- Reconstructing infectious disease transmission history often relies on pathogen genetic sequences, especially when medical records are scarce.
- Historical viral sequences enhance evolutionary estimates of epidemic history, particularly for viruses like HIV and hepatitis C virus (HCV) that circulated long before identification.
- Few pre-1989 HCV isolates are available, limiting historical evolutionary analyses.
Purpose of the Study:
- To report and analyze two subgenomic HCV sequences from 1953, representing the oldest genetic evidence of HCV infection.
- To use these historical sequences to estimate the common ancestor of HCV in the USA and explore transmission history.
- To validate the evolutionary information from historical sequences using a novel phylogenetic molecular clock method.
Main Methods:
- Analysis of two HCV subgenomic sequences obtained from infected individuals in 1953.
- Phylogenetic analysis to estimate pairwise genetic diversity and infer transmission history.
- Application of a new phylogenetic molecular clock method to estimate sampling dates of archived and contemporary viral genomes.
Main Results:
- The two 1953 HCV sequences represent the oldest genetic evidence of HCV infection.
- Pairwise genetic diversity suggests substantial HCV transmission occurred before the 1950s.
- Phylogenetic analysis incorporating these sequences provided new estimates for the common ancestor of HCV in the USA, with statistical uncertainty noted.
Conclusions:
- The 1953 archived HCV sequences are consistent with their proposed sampling date, despite large statistical uncertainty.
- High evolutionary rate heterogeneity and star-like phylogeny may introduce bias and reduce statistical power in dating historical viruses.
- These findings highlight challenges and potential improvements for dating historical viral pathogens using limited genetic data.
Related Concept Videos
00:36Viral Mutations
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
02:33Retroviruses
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
01:25Hepatitis
Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
01:28Viral Hepatitis I: Introduction
Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...
01:10Retrovirus Life Cycles
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
01:08Evolution of Microbial Genome
Microbial genome evolution is a highly dynamic process shaped by continual gene gain and loss across species and strains. This genomic flexibility allows microorganisms to adapt rapidly to environmental pressures and interactions with other organisms. Central to understanding this diversity is the distinction between the core and pan genomes.The core genome comprises the genes shared by all sampled strains of a species, representing essential functions needed for fundamental cellular processes.