Human retroviral antisense mRNAs are retained in the nuclei of infected cells for viral persistence

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  • Guangyong Ma
    Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing 210009, China;
  • Jun-ichirou Yasunaga
    Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;
  • Kazuya Shimura
    Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;
  • Keiko Takemoto
    Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;
  • Miho Watanabe
    Department of Hematology, Rheumatology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan
  • Masayuki Amano
    Department of Hematology, Rheumatology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan
  • Hirotomo Nakata
    Department of Hematology, Rheumatology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan
  • Benquan Liu
    Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing 210009, China;
  • Xiaorui Zuo
    Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing 210009, China;
  • Masao Matsuoka
    Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;

説明

<jats:title>Significance</jats:title> <jats:p> Two deadly human retroviruses, human T cell leukemia virus type 1 (HTLV-1) and HIV type 1 (HIV-1), enter latency in vivo, rendering viral countermeasures ineffective. Recently, novel retroviral genes have been discovered to be expressed from the antisense strand of retroviruses even during latency; they are called antisense genes, including the <jats:italic>HBZ</jats:italic> gene for HTLV-1 and <jats:italic>ASP</jats:italic> gene for HIV-1. We employed RNA-fluorescence in situ hybridization technology and discovered that human retroviral antisense messenger RNAs (mRNAs) are predominantly localized in the nucleus of infected cells, despite their coding function. Moreover, human retroviral antisense mRNAs are constantly expressed in latent retroviruses and retained in nucleus to support retroviral persistence; this may allow them to become novel feasible targets for retrovirus elimination. </jats:p>

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