Subclinical endometritis in dairy heifers experimentally infected with bovine gammaherpesvirus 4

Subclinical endometritis (SE) poses a substantial obstacle to reproductive efficiency in dairy cattle. Although bovine gammaherpesvirus 4 (BoGHV-4) has been associated with reproductive disturbances, its direct etiopathogenic role within the bovine endometrium remains inadequately elucidated. This study investigated the histopathological and immunological responses in the endometrium of dairy heifers experimentally infected via intrauterine inoculation with a local strain of BoGHV-4 (07/435) under controlled conditions. Seven animals were inoculated with BoGHV-4, while three served as uninfected controls. Over a 28-day period, assessments including clinical examinations, serology, histopathology, and immunohistochemistry were performed at designated intervals on days 0, 7, and 21 post-inoculation. Clinical signs were not observed, and systemic viral dissemination was not detected. Uterine biopsies displayed an acute, self-limiting, and highly localized inflammatory response, characterized by periglandular infiltration of CD68⁺ macrophages, CD3⁺ T lymphocytes, and CD79⁺ B lymphocytes. Immunological activation peaked at day 7 and resolved by day 21. Additionally, seroconversion was documented exclusively in two BoGHV-4-infected heifers by day 21, whereas all controls remained seronegative. Transient viral shedding in cervico-vaginal mucus was observed in the infected cohort. These findings provide novel experimental evidence that BoGHV-4 can induce a localized immune response within the bovine endometrium in the absence of overt clinical manifestations, acting as a subclinical modulator of the uterine microenvironment. This model advances our understanding of virus-host interactions in reproductive tissues and emphasizes the importance of considering subclinical viral infections in diagnostic and reproductive management strategies within dairy herds.