Single-Genome Sequencing of Hepatitis C Virus in Donor-Recipient Pairs Distinguishes Modes and Models of Virus Transmission and Early Diversification
- Univ. of Pennsylvania, Philadelphia, PA (United States). Dept. of Medicine and Microbiology
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). T-Division
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). T-Division; Stanford Univ., CA (United States). Dept. of Biology
- National Inst. of Health (NIH), Bethesda, MD (United States). Dept. of Transfusion Medicine
- Univ. of California, San Francisco, CA (United States). Blood Systems Research Inst.
- Icahn School of Medicine at Mount Sinai, New York, NY (United States). Division of Infectious Diseases
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). T-Division; Santa Fe Inst. (SFI), Santa Fe, NM (United States)
Despite the recent development of highly effective anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and development of an effective vaccine. A precise molecular identification of transmitted/founder (T/F) HCV genomes that lead to productive clinical infection could play a critical role in vaccine research, as it has for HIV-1. However, the replication schema of these two RNA viruses differ substantially, as do viral responses to innate and adaptive host defenses. These differences raise questions as to the certainty of T/F HCV genome inferences, particularly in cases where multiple closely related sequence lineages have been observed. To clarify these issues and distinguish between competing models of early HCV diversification, we examined seven cases of acute HCV infection in humans and chimpanzees, including three examples of virus transmission between linked donors and recipients. Using single-genome sequencing (SGS) of plasma vRNA, we found that inferred T/F sequences in recipients were identical to viral sequences in their respective donors. Early in infection, HCV genomes generally evolved according to a simple model of random evolution where the coalescent corresponded to the T/F sequence. Closely related sequence lineages could be explained by high multiplicity infection from a donor whose viral sequences had undergone a pretransmission bottleneck due to treatment, immune selection, or recent infection. These findings validate SGS, together with mathematical modeling and phylogenetic analysis, as a novel strategy to infer T/F HCV genome sequences.
- Research Organization:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- Grant/Contract Number:
- AC52-06NA25396
- OSTI ID:
- 1626075
- Journal Information:
- Journal of Virology, Vol. 90, Issue 1; ISSN 0022-538X
- Publisher:
- American Society for MicrobiologyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Clearance of hepatitis C virus is associated with early and potent but narrowly-directed, Envelope-specific antibodies
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journal | September 2019 |
High multiplicity of infection following transplantation of hepatitis C virus–positive organs
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journal | June 2019 |
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