engleski

Female Sex Hormones Modulate the Course of MCMV Infection

Objective: Sex steroid hormones influence the components of both innate and adaptive immunity, resulting in differences of immune responses between genders. Moreover, hormonal changes associated with pregnancy modify the severity of some infections and diseases. Progesteron has been proved as an inhibitor of antiviral immunity in both human and animal studies. Cytomegalovirus (CMV), a hepesvirus, is a ubiquitous pathogen and can be isolated from all body fluids of patients undergoing primary infection. CMV infection in gonads is predominantly described in immunocompromised patients and its role in gonadal insufficiency is still not completely elucidated. The aim of this study was to test whether sex hormones change the course and immunosurveillance of murine CMV (MCMV) infection in BALB/c mice. Methods: Female mice were treated with PMSG and hCG to trigger ovulation and luteinization. Virgin animals as well as pregnant ones were intravenously infected with MCMV and sacrificed daily from 1st to 10th day post infection. Viral titers in various organs were analyzed using a standard plaque forming assay. Virus spread was examined using immunohistochemistry. Progesterone levels in plasma were measured using Progesterone EIA kit. Results: MCMV successfully infected ovarian tissue in immunocompetent mice. Numerous infected cells were detected predominantly in corpora lutea, while follicles were free from infection. Our results showed higher susceptibility of pregnant mice to MCMV infection in various organs examined, while ovaries of pregnant mice showed delay in clearance of productive infection as compared to non-pregnant animals. The infection induced a strong innate immune response in corpora lutea which was predominantly comprised of infiltrating macrophages, while CD4+ and CD8+ T cells seemed to play a minor role. Increased plasma progesterone levels were observed in infected mice as compared to controls. Conclusions: Our study provides a new insight into the pathogenesis of MCMV infection in female reproductive tissue as well as its dependence on sex steroid environment. An elevated progesterone level underpins virus replication. These findings could bring evidence for the role of CMV infection in the pathogenesis of gonadal dysfunction.

Sex hormone; MCMV modulation

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