Speaker
Description
The infected blood inquiry (IBI) carried out by the UK Government examined the incidence of mass contamination of human plasma-derived commercial clotting factors between 1970 and the early 1990’s. The inquiry demonstrated that numerous viruses, including HIV and hepatitis C virus, were transmitted via contaminated blood and blood-products. While limited understanding of bloodborne viruses during this period resulted in an underappreciated impact of the use of infectious material, the diversity and quantity of viral material present in these contaminated products remains incompletely understood. Recent work using modern PCR-based detection provided an insight into eight viruses present in 24 archived clotting factors from 1974 to 1992. Here we deployed a custom-designed oligonucleotide bait panel, which targeted over 100 viral species, to carry out targeted metagenomic sequencing of the 24 archived clotting factor samples. Our aim was to compare the effects of viral inactivation and blood safety measures implemented from 1974 to 1992 on the genomic composition of human-derived medicines. Targeted metagenomics recovered sequence data for multiple viruses and identified viral genotypes present in the archived samples. The genomic data was used to reconstruct time-resolved phylogenies for recovered HIV-1, hepatitis C virus, human pegivirus, and parvoviruses 4 and B19, and to assess the impact of blood safety measures discussed in the IBI on the presence of different viral genotypes. We identified diverse intra-species virus populations within the archived human-derived clotting factors. Future work will include the deconvolution of blood-borne viruses to determine the number of infected donors and characterise intra-sample genotype diversity.
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