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- Title
High multiplicity infection following transplantation of hepatitis C virus-positive organs.
- Authors
Zahid, Muhammad N.; Shuyi Wang; Learn, Gerald H.; Abt, Peter L.; Blumberg, Emily A.; Reese, Peter P.; Goldberg, David S.; Shaw, George M.; Bar, Katharine J.; Wang, Shuyi
- Abstract
Highly effective direct-acting antivirals against Hepatitis C virus (HCV) have created an opportunity to transplant organs from HCV-positive individuals into HCV-negative recipients, since de novo infection can be routinely cured. As this procedure is performed more widely, it becomes increasingly important to understand the biological underpinnings of virus transmission, especially the multiplicity of infection. Here, we used single genome sequencing of plasma virus in four genotype 1a HCV-positive organ donors and their seven organ recipients to assess the genetic bottleneck associated with HCV transmission following renal and cardiac transplantation. In all recipients, de novo infection was established by multiple genetically distinct viruses that reflect the full phylogenetic spectrum of replication-competent virus circulating in donor plasma. This was true in renal and cardiac transplantation and in recipients with peak viral loads ranging between 2.9 and 6.6 log10 IU/mL. The permissive transmission process characterized here contrasts sharply with sexual or injection-related transmission, which occurs less frequently per exposure and is generally associated with a stringent genetic bottleneck. These findings highlight the effectiveness of current anti-HCV regimens, while raising caution regarding the substantially higher multiplicity of infection seen in organ transplantation-associated HCV acquisition.
- Subjects
ORGAN donor registries; MULTIPLICITY (Mathematics); TRANSPLANTATION of organs, tissues, etc.; HEPATITIS C virus; HEPATITIS; INFECTION; KIDNEY transplantation; HEPATITIS C transmission; COMPARATIVE studies; BIOLOGICAL evolution; HEART transplantation; HEPATITIS C; HEPATITIS viruses; IMMUNITY; RESEARCH methodology; MEDICAL cooperation; RESEARCH; EVALUATION research
- Publication
Journal of Clinical Investigation, 2019, Vol 129, Issue 8, p3134
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI127203