title: miR-28-3p is a cellular restriction factor that inhibits human T cell leukemia virus, type 1 (HTLV-1) replication and virus infection.
abstract: Human T cell leukemia virus, type 1 (HTLV-1) replication and spread are controlled by different viral and cellular factors. Although several anti-HIV cellular microRNAs have been described, such a 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. Because miR-28-3p is highly expressed in resting T cells, which are resistant to HTLV-1 infection, we investigated a potential protective role of miR-28-3p against de novo HTLV-1 infection. To this end, we developed a new sensitive and quantitative assay on the basis of 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 the transmission of the virus has shown that the ATK-1 strain, which carries a Thr-to-Cys transition mutation, is transmitted efficiently between spouses, suggesting that miR-28 may play an important role in HTLV-1 transmission.
authors.affiliation: From the University of Kansas Medical Center, Department of Pathology and Laboratory Medicine and Center for Viral Oncology, Kansas City, Kansas 66160.
authors.forename: Xue Tao
authors.initials: XT
authors.lastname: Bai
authors.affiliation: From the University of Kansas Medical Center, Department of Pathology and Laboratory Medicine and Center for Viral Oncology, Kansas City, Kansas 66160 cnicot@kumc.edu.
authors.forename: Christophe
authors.initials: C
authors.lastname: Nicot
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D015490:HTLV-I Infections / Q000235:genetics* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000235:genetics*
chemical_list: D015685:Fusion Proteins, gag-pol; C570628:MIRN28 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral
keywords: HTLV-1; Host Defense; Leukemia; MicroRNA (miRNA); Virology; Virus Entry; Virus Infection; Virus Replication