W. Austin J. Guild

Conference 2022 Live Talk


Talk title

Endogenous retroviruses induce protective host immunity against HSV-2 vaginal infection in mice


Authors and Affiliations

Maria Tokuyama1, Radeesha Jayewickreme2, Tianyang Mao2, William Philbrick2, Yong Kong2, Rebecca Treger2, Tasfia Rakib2, Huiping Dong2, May Dang-Lawson1, Tatiana Lau1, W. Austin Guild1, Akiko Iwasaki2

1. University of British Columbia, Canada.
2. School of Medicine, Yale University, United States.




Herpes simplex 2 (HSV-2) is endemic in many countries, and in 2016, it was estimated that 491.5 million people worldwide were infected with HSV-2. In addition to uncomfortable reoccurring symptoms, people infected with HSV-2 are more likely to contract HIV. Currently, there is no cure for HSV-2, and thus, it is important to have a deeper understanding of the host immune response to HSV-2. Endogenous retroviruses (ERVs) make up approximately 8% of the human genome and originated from exogenous retrovirus infection of non-human primates over 100 million years ago. ERVs are capable of modulating the immune system, and they can also prevent exogenous viral infections. Therefore, we sought to test the hypothesis that high levels of ERV expression in mice would protect mice against intravaginal HSV-2 infection.


To test this hypothesis, we compared mice expressing high levels of ERVs (Toll-like receptor 7-deficient, Tlr7-/-), Tlr7-/- mice deficient in ERVs (Tlr7-/-Emv2-/-), Emv2-/- mice, and wildtype C57BL/6 (B6) mice. All four strains were infected intravaginally with HSV-2, and disease scores were determined for two weeks post HSV-2 infection. We also treated B6 mice and type I IFN receptor-deficient (IFNAR-/-) mice with exogenous ERVs intravaginally prior to HSV-2 infection to determine if ERVs are sufficient to provide protection and whether type I IFN signalling is required for the protection.


We found that Tlr7-/- mice that expressed high levels of ERVs had lower disease scores post HSV-2 infection compared to all other strains of mice that lacked ERV expression. In addition, B6 mice intravaginally treated with exogenous ERVs prior to HSV-2 infection had lower disease scores compared to untreated mice. Finally, IFNAR-/-mice treated intravaginally with ERVs prior to HSV-2 infection also showed reduced disease score compared to untreated mice infected with HSV-2.


Our data revealed that ERVs modulate host immunity against HSV-2 vaginal infection in mice, leading to less severe disease. This reduction in disease severity is not dependent on a type I IFN response. For future directions, we will determine the mechanism of ERV-mediated protection against HSV-2 vaginal infection. These studies contribute to further understanding antiviral response against HSV-2 and to the development of new therapeutics in the future.