miR-28-3p is a cellular restriction factor that inhibits HTLV-1 replication and virus infection. [Molecular Bases of Disease]

January 7th, 2015 by Bai, X. T., Nicot, C.

Human retrovirus HTLV-1 replication and spread are controlled by different viral and cellular factors. Although several anti-HIV cellular microRNAs have been described, such regulation for HTLV-1 has not been reported. In this study, we found that miR-28-3p inhibits HTLV-1 virus expression and its replication by targeting a specific site within the genomic gag/pol viral mRNA. Since miR-28-3p is highly expressed in resting T cells, which are resistant to HTLV-1 infection, we investigate a potential protective role of miR-28-3p against de novo HTLV-1 infection. To this end, we develop a new sensitive and quantitative assay based on the detection of products of reverse transcription. We demonstrate that miR-28-3p does not prevent virus receptor interaction or virus entry but instead induces a post-entry block at the reverse transcription level. In addition, we found that HTLV-1 subtype 1A isolates, corresponding to the Japanese strain ATK-1, present a natural single nucleotide polymorphism within the miR-28-3p target site. As a result of this polymorphism, the ATK-1 virus sequence was not inhibited by miR-28. Interestingly, genetic studies on transmission of virus had shown that the ATK-1 strain, which carries a T-to-C transition mutation, was efficiently transmitted between spouses, suggesting that miR-28 may play an important role in HTLV-1 transmission.