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Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot results.

Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot results.
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Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh KR, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, Okayama A, Miura K, Satake M, Saito S, Itabashi K, Yamaguchi K, Kuroda M, Watanabe T, Okuma K, Hamaguchi I,


Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh KR, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, Okayama A, Miura K, Satake M, Saito S, Itabashi K, Yamaguchi K, Kuroda M, Watanabe T, Okuma K, Hamaguchi I, (click to view)

Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh KR, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, Okayama A, Miura K, Satake M, Saito S, Itabashi K, Yamaguchi K, Kuroda M, Watanabe T, Okuma K, Hamaguchi I,

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Journal of clinical microbiology 2017 07 12() pii 10.1128/JCM.00659-17

Abstract

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.

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