Journal of clinical microbiology 2017 07 12() pii 10.1128/JCM.00659-17
Western blot (WB) for human T cell leukemia virus type 1 is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of WB-indeterminate results by analyzing the genomic sequences of HTLV-1 provirus. Quantitative PCR measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 vs 0.71). Phylogenic analysis of the complete HTLV-1 genome of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions, composed of four types, G-to-A (29%), C-to-T (19%), T-to-C (19%), and A-to-G (16%). In the most frequent G-to-A substitution, 64% occurred at GG dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB-indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings suggest that WB-indeterminate carriers have low production of viral antigens due to the combination of low proviral load and mutations in the provirus, which may interfere with the host recognition to HTLV-1 antigens.