HN1L is essential for cell growth and survival during nucleopolyhedrovirus infection in silkworm, Bombyx mori

PLoS One. 2019 May 22;14(5):e0216719. doi: 10.1371/journal.pone.0216719. eCollection 2019.

Abstract

Hematological and neurological expressed 1-like (HN1L) protein is an evolutionarily conserved protein that plays an important role in embryonic development. It has been reported that HN1L is involved in the process of cell growth and cancer formation and that cell cycle arrest occurs during suppression of HN1L expression. Previous studies have demonstrated that the expression levels of the Bombyx mori HN1L protein were significantly downregulated in Bombyx mori Nucleopolyhedrovirus (BmNPV) infected silkworm cells. Transient transfections were performed with plasmids for pIEX-1-HN1L expression in Bombyx mori ovarian cells (BmN) in order to explore the effect of the HN1L protein on the growth of silkworm cells and its regulatory role in the process of viral infection. Cellular localization analysis revealed that HN1L was localized in the cytoplasm and that its upregulation could significantly enhance cellular activity. Furthermore, HN1L could promote G1/S phase conversion, thereby contributing to cell proliferation. Upon infection of BmN cells with BmNPV, the induction of apoptosis increased, although HN1L overexpression could inhibit DNA fragmentation, suggesting that the HN1L protein could inhibit cell apoptosis induced by viral invasion. In addition, Western blotting indicated that the HN1L protein inhibited the activation of caspase-9 zymogen and the expression of Bax protein, although it promoted Bcl-2 expression. Flow cytometry analysis further confirmed that overexpression of HN1L significantly inhibited apoptosis induced by BmNPV infection. Consequently, we demonstrated that BmN HN1L is a protein with multiple functions, which enhanced cell activity, regulated the cell cycle and induced an anti-apoptotic response by BmNPV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bombyx / cytology
  • Bombyx / physiology
  • Bombyx / virology*
  • Cell Cycle
  • Cell Proliferation / physiology
  • Cell Survival / physiology
  • Genes, Insect
  • Host Microbial Interactions / genetics
  • Host Microbial Interactions / physiology
  • Insect Proteins / genetics
  • Insect Proteins / physiology*
  • Nucleopolyhedroviruses / pathogenicity*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Insect Proteins
  • Recombinant Proteins

Supplementary concepts

  • Bombyx mori nucleopolyhedrovirus

Grants and funding

This work was supported by the Natural Science Foundation of Zhejiang Province (No. LY17C170006) and National High-tech R&D program (863 Program) (No. 2011AA100603). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.