Effect of Bluetongue Virus Serotype 1 Infection During Late-stage of Gestation in IFNAR1-blocked Immunocompetent Mouse Model

Bluetongue (BT) is an economically significant viral disease caused by bluetongue virus (BTV). BTV is spread by arthropods, which affects domestic and wild animals. In fetal ruminants, BTV exhibits neurotropism, leading to abortion and congenital defects in brain especially in cattle and sheep when infected in utero. Transplacental transmission (TPT) of wild Indian BTV-1 in late pregnancy has never been proven experimentally. This study is the first to demonstrate TPT of wild Indian BTV-1 during late pregnancy using an immunocompetent mouse model of IFNAR1 blockade. The present study examines sequential pathology, developmental anomalies, demonstration of BTV-1 antigen localization in the reproductive organs, haematological and biochemical alterations, and humoral immunity during the late stage of gestation. During late stage of gestation, the rate of TPT was notably higher at 80.00%. Clinical signs became increasingly noticeable in dams from 5 dpi onward, including symptoms such as abortion, anorexia, ocular discharge, and huddling tendency. Reduced growth rate, rough hair coat, and head tilting due to nervous signs were observed in 10-day-old fetuses. BTV-1 infection during the late stage of gestation caused abortion, maceration, necro-haemorrhagic lesions in reproductive organs, hemorrhages in foetal organs, and non-significantly decreased bone size (Alizarin red staining) in fetuses. Perivascular hemorrhages due to endothelial damage in lungs, interstitial pneumonia and meningitis were observed in 10-day-old fetuses. BTV-infected pregnant mice showed leukopenia with lymphopenia and seroconversion by 6 dpi (21 days of gestation). Further, significant alterations in serum biochemical values were observed when compared them to those of the uninfected control group. BTV-1 antigen was demonstrated in foetuses, placenta, uterus, and ovaries using immunohistochemistry and RT-PCR. This mouse model presents a suitable platform for studying the mechanisms underlying transplacental transmission.