Human retroviral antisense mRNAs are retained in the nuclei of infected cells for viral persistence
Guangyong Ma, Jun‐ichirou Yasunaga, Kazuya Shimura, Keiko Takemoto, Miho Watanabe, Masayuki Amano, Hirotomo Nakata, Benquan Liu, Xiaorui Zuo, Masao Matsuoka
Abstract
Significance 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 HBZ gene for HTLV-1 and ASP 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.