HLA-DMB restricts human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG7 acetylation

Sci Rep. 2017 Oct 31;7(1):14416. doi: 10.1038/s41598-017-14882-z.

Abstract

The roles of autophagy in viral infection are complicated. While autophagy has been shown to function in host antiviral defense by eliminating intracellular viruses and regulating adaptive immunity, several viruses have evolved molecular mechanisms to get benefits from it. The deltaretrovirus human T-cell leukemia virus type-1 (HTLV-1) has been reported to profit its replication from enhancing autophagosome accumulation. Here, we reported that HLA-DMB (generally referred to here as DMB), the beta chain of the non-classical MHC-II protein HLA-DM, had strong expression in HTLV-1-transformed T-cell lines and could be induced in Hela, PMA-differentiated THP1 (PMA-THP1) or primary human monocytes by HTLV-1 infection. Immunoblot and real-time PCR assays demonstrated that overexpression of DMB decreased HTLV-1 protein expression while the knockdown of DMB increased HTLV-1 protein expression. Immunoblot and confocal microscopy assays indicated that overexpression of DMB decreased HTLV-1 induced autophagosome accumulation while the knockdown of DMB yielded the opposite effects. Coimmunoprecipitation and immunoprecipitation experiments suggested DMB interacted with autophagy-related gene (ATG) 7 and increased the acetylation of ATG7. Taken together, these results suggested DMB modulated HTLV-1 protein expression through regulation of autophagosome accumulation and our findings suggested a new mechanism by which the host cells defended against HTLV-1 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Autophagy
  • Autophagy-Related Protein 7 / genetics
  • Autophagy-Related Protein 7 / metabolism
  • Autophagy-Related Protein 7 / physiology
  • Cell Line
  • HEK293 Cells
  • HLA-D Antigens / metabolism
  • HLA-D Antigens / physiology*
  • HeLa Cells
  • Human T-lymphotropic virus 1 / genetics*
  • Human T-lymphotropic virus 1 / immunology*
  • Human T-lymphotropic virus 1 / metabolism
  • Humans
  • Monocytes / immunology
  • Primary Cell Culture
  • Protein Binding
  • Protein Processing, Post-Translational

Substances

  • HLA-D Antigens
  • HLA-DM antigens
  • Atg7 protein, human
  • Autophagy-Related Protein 7