Multiple subtypes of coxsackievirus group B can cause congenital heart disease

Abstract

Background: Different serotypes of coxsackievirus B (CVB), which is the most common cause of viral myocarditis, target cardiomyocytes through Coxsackie and Adenovirus Receptor and Decay-Accelerating Factor. Both receptors are expressed in the fetal heart. We hypothesized that infection with different serotypes of CVB during early pregnancy plays a role in pathogenesis of congenital heart defect (CHD).Methods: In this study, we use a murine model to infect with CVB1, CVB4, and combination of CVB3 + CVB4 during a critical period in gestation. We examined offspring of pregnant mice for fetal death and heart defects following viral infection. Result: Fetuses from uninfected control dams showed normal heart development, while maternal CVB infection precipitates CHD: majorly ventricular septal defects (VSD) and non-compaction of ventricular myocardium (NC), with some infrequent cases of double outlet right ventricle, left ventricle wall rupture, right ventricle hypertrophy, and thickened/dysplastic semilunar valves. Infection of pregnant dams with CVB1 leads to 44% VSD and 41.2% NC cases, while with CVB4 leads to 31.7% VSD and 13.3% NC cases. Co-infection with CVB3 + CVB4 increases fetal pathology to 51.3% VSD and 41% NC cases.Infection can also result in fetal death, with higher incidences with CVB3 + CVB4 with 46.2% cases, compared to 33.3% by CVB1 and 21.7% by CVB4. Male fetuses were more susceptible to all phenotypes. Conclusion:Our report shows that prenatal CVB infections can lead to pathogenesis of certain heart defects in mouse model, particularly exacerbated with co-infections. This data confirms a link between prenatal CVB infection and CHD development and highlights it is not unique to just one serotype of CVB.

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening

“…This condition has become a serious public health concern worldwide, particularly in the Asia-Pacific region ( Bian et al., 2019 ). According to epidemiological data from the past decade, group A enterovirus (EV)-A71, coxsackievirus (CV)-A16, CV-A6, CV-A10 and group B CV-B3 and CV-B5 virus are the main pathogens responsible for HFMD ( Wang et al., 2022 ), severe viral myocarditis and aseptic meningitis ( Saguil et al., 2019 ; Zhang X. et al., 2022 ; Sharma et al., 2023 ). Although three inactivated EV-A71 vaccines have been available to combat HFMD ( Bello and Roshorm, 2022 ; Kinobe et al., 2022 ), persistent epidemics and cross-infections continue to pose huge threats to public health.…”