Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors

Immunity. 2012 Nov 16;37(5):867-79. doi: 10.1016/j.immuni.2012.07.018. Epub 2012 Nov 8.


The genome of vertebrates contains endogenous retroviruses (ERVs) that are largely nonfunctional relicts of ancestral germline infection by exogenous retroviruses. However, in some mouse strains ERVs are actively involved in disease. Here we report that nucleic acid-recognizing Toll-like receptors 3, 7, and 9 (TLR 3, TLR7, and TLR9) are essential for the control of ERVs. Loss of TLR7 function caused spontaneous retroviral viremia that coincided with the absence of ERV-specific antibodies. Importantly, additional TLR3 and TLR9 deficiency led to acute T cell lymphoblastic leukemia, underscoring a prominent role for TLR3 and TLR9 in surveillance of ERV-induced tumors. Experimental ERV infection induced a TLR3-, TLR7-, and TLR9-dependent group of "acute-phase" genes previously described in HIV and SIV infections. Our study suggests that in addition to their role in innate immunity against exogenous pathogens, nucleic acid-recognizing TLRs contribute to the immune control of activated ERVs and ERV-induced tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / genetics
  • Antibodies, Viral / immunology
  • Cell Line
  • Endogenous Retroviruses / genetics*
  • Endogenous Retroviruses / immunology
  • Endogenous Retroviruses / metabolism
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nucleic Acids / genetics*
  • Nucleic Acids / immunology
  • Nucleic Acids / metabolism
  • Oncogenes / genetics
  • Oncogenes / immunology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Toll-Like Receptors / genetics*
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism*
  • Viremia / genetics*
  • Viremia / immunology
  • Viremia / metabolism


  • Antibodies, Viral
  • Nucleic Acids
  • Toll-Like Receptors