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Endogenous MMTV proviruses induce susceptibility to both viral and bacterial pathogens

Sanchita Bhadra1, Mary M Lozano, Shelley M Payne

  • 1Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America.

Plos Pathogens
|December 5, 2006
PubMed

Insights

Mice lacking endogenous mouse mammary tumor viruses (Mtvs) show resistance to specific viral and bacterial infections. Endogenous Mtvs, particularly those encoding superantigens (Sags), confer genetic susceptibility to pathogens.

Area of Science:

  • Immunology
  • Virology
  • Microbiology
  • Genetics

Background:

  • Most inbred mice harbor endogenous mouse mammary tumor virus (MMTV) proviruses (Mtvs) with replication defects.
  • Endogenous retroviruses and their encoded superantigens (Sags) are implicated in host-pathogen interactions.
  • The role of endogenous Mtv proviruses in innate resistance to pathogens is not fully understood.

Purpose of the Study:

  • To investigate the role of endogenous mouse mammary tumor viruses (Mtvs) in host susceptibility to MMTV and bacterial infections.
  • To determine if resistance in Mtv-null mice is dependent on superantigen (Sag) expression.
  • To explore the broader implications of endogenous retroviral Sags for pathogen-induced responses.

Main Methods:

  • Comparison of MMTV infection and tumorigenesis in Mtv-null BALB/c mice versus wild-type BALB/c mice.
  • Infection of Mtv-null mice with an MMTV-related retrovirus to assess T-cell lymphoma induction.
  • Intragastric inoculation of Gram-negative bacteria (Vibrio cholerae and Salmonella typhimurium) in Mtv-null and wild-type mice.
  • Reconstitution experiments by introducing specific endogenous Mtvs into Mtv-null mice.

Main Results:

  • Mtv-null mice exhibited resistance to MMTV infection, tumorigenesis, and MMTV-related retrovirus-induced lymphomas.
  • Resistance was not dependent on superantigen (Sag) expression.
  • Mtv-null mice were resistant to Vibrio cholerae-induced mortality but showed similar susceptibility to Salmonella typhimurium compared to wild-type mice.
  • Presence of specific endogenous Mtvs reconstituted susceptibility to MMTV and V. cholerae, correlating with increased pathogen load.
  • One endogenous Mtv provirus encoding only Sag was sufficient to confer susceptibility.

Conclusions:

  • Endogenous Mtv-encoded superantigens (Sags) confer a unique genetic susceptibility to specific viral and bacterial pathogens.
  • These findings highlight the significant impact of endogenous retroviruses on host-pathogen interactions.
  • The study suggests broad implications for understanding pathogen-induced responses in both mice and humans, given the presence of human endogenous retroviruses encoding Sags.

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