Full annotation of serum virome in Chinese blood donors with elevated alanine aminotransferase levels

BACKGROUND A serum alanine aminotransferase (ALT) test is currently demanded for blood donation in China. One of the major reasons to include such a test is possible etiology of known or unknown hepatotropic viruses. However, this hypothesis has never been examined convincingly. STUDY DESIGN AND METHODS The study recruited 90 Chinese blood donors that were divided into three groups based on their ALT values. Serum virome from these donors was explored using a metagenomics approach with enhanced sensitivity resolved at single sequencing reads. RESULTS Anellovirus and pegivirus C (GBV-C) were detected among these donors. None of them were found solely in donors with abnormal liver enzyme. Anellovirus was highly prevalent (93.3%) and the co-infection with multiple genera (alpha, beta, and gammatorquevirus) were more common in the donors with normal ALT values in comparison to those with elevated ALT (single/double/triple Anellovirus genera, 1/3/24 vs. 7/7/14 or 6/7/13, p = 0.009). For unmapped reads that accounted for 15 +/- 14.9% of the data, similarity-based (BLASTN, BLASTP, and HMMER3) and similarity-independent (k-mer frequency) analysis identified several circular rep encoding ssDNA (CRESS-DNA) genomes. Direct PCR testing indicated these genomes were likely reagent contaminants. CONCLUSION Viral etiology is not responsible for elevated ALT levels in Chinese blood donors. The ALT test, if not abandoned, should be adjusted for its cutoff in response to donor shortage in China.