Frontiers in Microbiology (Nov 2021)

An Endogenous Retroviral LTR-Derived Long Noncoding RNA lnc-LTR5B Interacts With BiP to Modulate ALV-J Replication in Chicken Cells

  • Shihao Chen,
  • Shihao Chen,
  • Shihao Chen,
  • Ruihan Zhao,
  • Ruihan Zhao,
  • Ting Wu,
  • Ting Wu,
  • Dedong Wang,
  • Dedong Wang,
  • Biao Wang,
  • Biao Wang,
  • Shiyu Pan,
  • Shiyu Pan,
  • Xuming Hu,
  • Xuming Hu,
  • Zhiming Pan,
  • Hengmi Cui,
  • Hengmi Cui,
  • Hengmi Cui

DOI
https://doi.org/10.3389/fmicb.2021.788317
Journal volume & issue
Vol. 12

Abstract

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Infection with the avian leukosis virus subgroup J (ALV-J) impairs host genes and facilitates the establishment of chronic infection and the viral life cycle. However, the involvement of long noncoding RNAs (lncRNAs) in ALV-J infection remains largely unknown. In this study, we identified a novel chicken lncRNA derived from LTR5B of the ERV-L family (namely lnc-LTR5B), which is significantly downregulated in ALV-J infected cells. lnc-LTR5B was localized in the cytoplasm and was relatively high expressed in the chicken lung and liver. Notably, the replication of ALV-J was inhibited by the overexpression of lnc-LTR5B but enhanced when lnc-LTR5B expression was knocked down. We further confirmed that lnc-LTR5B could bind to the binding immunoglobulin protein (BiP), a master regulator of endoplasmic reticulum (ER) function. Mechanistically, lnc-LTR5B serves as a competing endogenous RNA for BiP, restricting its physical availability. Upon ALV-J infection, the reduction of lnc-LTR5B released BiP, which facilitated its translocation to the cell surface. This is crucial for ALV-J entry as well as pro-survival signaling. In conclusion, we identified an endogenous retroviral LTR-activated lnc-LTR5B that is involved in regulating the cell surface translocation of BiP, and such regulatory machinery can be exploited by ALV-J to complete its life cycle and propagate.

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