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Dampened antiviral immunity to intravaginal exposure to RNA viral pathogens allows enhanced viral replication

Shahzada Khan1, Erik M Woodruff1, Martin Trapecar1

  • 1Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158.

The Journal of Experimental Medicine
|November 18, 2016
PubMed

Insights

Vaginal exposure to RNA viruses like Zika virus causes minimal immune response, hindering viral control. Enhancing inflammation in vaginal tissue effectively inhibits viral replication and improves immune responses.

Area of Science:

  • Immunology
  • Virology
  • Reproductive Health

Background:

  • Sexual transmission of RNA viruses poses a significant public health challenge.
  • Understanding the female reproductive tract's immune response to viral pathogens is crucial for developing effective interventions.

Purpose of the Study:

  • To investigate the host immune response to vaginal RNA virus exposure.
  • To elucidate the mechanisms underlying viral replication and immune evasion in the vaginal mucosa.
  • To explore strategies for enhancing immune control of vaginal viral infections.

Main Methods:

  • Utilized mouse models with lymphocytic choriomeningitis virus (LCMV) and Zika virus (ZIKV) infections.
  • Assessed viral replication, interferon and inflammatory responses in the vaginal mucosa.
  • Evaluated antigen-presenting cell (APC) maturation and CD8 T cell responses.
  • Investigated the impact of enhanced innate inflammation on viral control.

Main Results:

  • RNA viruses replicate in the vaginal mucosa with minimal antiviral and inflammatory responses.
  • Dampened innate immunity and impaired APC maturation hinder viral control.
  • Enhancing vaginal mucosal inflammation inhibits ZIKV replication and rescues the immune phenotype.
  • Delayed CD8 T cell activation and impaired effector function contribute to prolonged viral presence.

Conclusions:

  • Vaginal tissue is highly susceptible to RNA virus infection due to a weak innate immune response.
  • Augmenting innate inflammation in the vaginal mucosa is a promising strategy to control viral replication.
  • The findings provide a framework for understanding male-to-female sexual transmission of viruses like ZIKV.

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