Illumination of Murine Gammaherpesvirus-68 Cycle Reveals a Sexual Transmission Route from Females to Males in Laboratory Mice

PLoS Pathogens

Pierre Drion¹  Philip G. Stevenson²  Laurent Gillet³  Sylvie François³  Alain Vanderplasschen³  Sarah Vidick³  Daniel Desmecht⁴  Mickaël Sarlet⁴ 

[1] Animal Facility (B23), GIGA-University of Liège, Liège, Belgium;Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom;Immunology-Vaccinology (B43b), Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium;Pathology (B43), Department of Morphology and Pathology, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium

关键词: Herpesviruses;    Sexually transmitted diseases;    Spleen;    Estrogens;    General anesthesia;    Luciferin;    Excretion;    Lymph nodes;   

DOI  :  10.1371/journal.ppat.1003292

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution. Gammaherpesviruses are archetypal pathogenic persistent viruses which have evolved to be transmitted in presence of specific immune response. Identifying their mode of transmission and their mechanisms of immune evasion is therefore essential to develop prophylactic and therapeutic strategies against these infections. As the known human gammaherpesviruses, Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus are host-specific and lack a convenient in vivo infection model; related animal gammaherpesviruses, such as murine gammaherpesvirus-68 (MHV-68), are commonly used as general models of gammaherpesvirus infections in vivo. To date, it has however never been possible to monitor viral excretion or virus transmission of MHV-68 in laboratory mice population. In this study, we have used MHV-68 associated with global luciferase imaging to investigate potential excretion sites of this virus in laboratory mice. This allowed us to identify a genital excretion site of MHV-68 following intranasal infection and latency establishment in female mice. This excretion occurred at the external border of the vagina and was dependent on the presence of estrogens. However, MHV-68 vaginal excretion was not associated with vertical transmission to the litter or with horizontal transmission to female mice. In contrast, we observed efficient virus transmission to naïve males after sexual contact. In vivo imaging allowed us to show that MHV-68 firstly replicated in penis epithelium and corpus cavernosum before spreading to draining lymph nodes and spleen. All together, those results revealed the first experimental transmission model for MHV-68 in laboratory mice. In the future, this model could help us to better understand the biology of gammaherpesviruses and could also allow the development of strategies that could prevent the spread of these viruses in natural populations.

【 授权许可】

CC BY