Viral infection of the ovaries compromises pregnancy and reveals innate immune mechanisms protecting fertility

Viral infections during pregnancy are a considerable cause of adverse outcomes and birth defects, and the underlying mechanisms are poorly understood. Among those, cytomegalovirus (CMV) infection stands out as the most common intrauterine infection in humans, putatively causing early pregnancy loss. We employed murine CMV as a model to study the consequences of viral infection on pregnancy outcome and fertility maintenance. Even though pregnant mice successfully controlled CMV infection, we observed highly selective, strong infection of corpus luteum (CL) cells in their ovaries. High infection densities indicated complete failure of immune control in CL cells, resulting in progesterone insufficiency and pregnancy loss. An abundance of gap junctions, absence of vasculature, strong type I interferon (IFN) responses, and interaction of innate immune cells fully protected the ovarian follicles from viral infection. Our work provides fundamental insights into the effect of CMV infection on pregnancy loss and mechanisms protecting fertility. [Display omitted] •Cytomegalovirus strongly infects all ovarian cells except follicular cells•Infection of corpus luteum compromises progesterone production and pregnancy•Blood follicle barrier and innate immune responses protect the follicles•IFNβ signaling is the main factor of follicular cell resistance Although viral infections are known risk factors during pregnancy, little is known about their effect on reproductive organs and fertility. Tomac et al. demonstrate how human cytomegalovirus infection of the ovaries could result in abortion and identifies immunological barriers protecting future fertility.