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Updated: Jul 30, 2026

Two Methods of Heterokaryon Formation to Discover HCV Restriction Factors
Published on: July 16, 2012
Drift in the hypervariable region of the hepatitis C virus during 27 years in two patients
Guang Gao1, Zelma Buskell, Leonard Seeff
1Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Food and Drug Administration, Bethesda, Maryland, USA.
Insights
Hepatitis C virus (HCV) transmission between a patient and nurse led to viral evolution. Early infection showed uniform HCV sequences, later evolving into diverse quasispecies within the host.
Area of Science:
- Virology
- Molecular Biology
- Epidemiology
Background:
- Hepatitis C virus (HCV) infection poses a significant global health challenge.
- Understanding HCV genetic diversity and evolution is crucial for developing effective treatments and prevention strategies.
Observation:
- Serial serum samples were collected over 27 years from an HCV-infected patient and a nurse with apparent transmission.
- HCV's hypervariable region 1 (HVR1) and 5'noncoding region (5'NCR) were analyzed using PCR and cloning.
- Early samples from both patient and nurse exhibited a predominant, common HVR1 sequence.
Findings:
- Later serum samples from both individuals revealed a heterogeneous mixture of HCV quasispecies.
- The initial uniformity of HVR1 sequences shifted to greater genetic diversity over time.
- This evolution suggests viral adaptation and diversification following HCV transmission and replication in a new host.
Implications:
- The study highlights the dynamic nature of HCV evolution post-transmission.
- Immune globulin administration to the nurse may have influenced observed HCV quasispecies changes.
- Findings contribute to understanding viral adaptation and host-pathogen interactions in HCV infection.
Abstract:
Serial serum samples were obtained over a 27-year period from a hepatitis C virus (HCV)-infected patient and from a nurse who appeared to become infected by this patient. The hypervariable region 1 (HVR1) and 5'noncoding region (5'NCR) of the HCV genome were amplified from each serum sample by polymerase chain reaction (PCR) and cloned. In the first serum specimen from the patient and the first two serum specimens from the nurse, most of the 20 clones from each serum sample had one common sequence in the HVR1 gene. All later serum samples contained a heterogeneous mixture of HCV quasispecies. The uniformity of the HVR1 sequence in the early samples and the emergence of greater diversity in later serum samples is consistent with the apparent transmission of HCV between the patient and nurse and the eventual emergence of other quasispecies as the virus replicated in the new host. In addition, the immune globulin given to the nurse may have been responsible for some of the HCV quasispecies changes observed in her serum.
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