Influence of Cryptosporidium and rotavirus co-infection on infectivity in calves

Rotavirus A (RVA; species <i>Rotavirus alphagastroenteritidis</i>) and <i>Cryptosporidium</i> spp. are major enteric pathogens in infants and neonatal calves, causing severe diarrhea that can lead to fatal outcomes. These pathogens thus pose challenges in both public health and the livestock industries. Although co-infections are common, their pathogenesis remains poorly understood. Here, we conducted a longitudinal investigation in naturally infected calves to assess the impact of co-infection with rotavirus and <i>Cryptosporidium</i>. Infection status was determined based on daily fecal antigen testing and oocyst per gram (OPG) counts from birth to 22 days of age. Based on these criteria, seven calves were classified as having <i>Cryptosporidium</i> mono-infection and three calves as having mixed infection. We found that subclinical infection with bovine rotavirus significantly shortened the duration of diarrhea caused by <i>Cryptosporidium parvum</i> in calves and reduced initial oocyst shedding. Furthermore, <i>in vitro</i> experiments using the bovine intestinal epitheliocyte (BIE) cell line demonstrated that the BRV Lincoln strain (G6, P[1]) non-structural protein 4 (NSP4) inhibits <i>C. parvum</i> infection, possibly by interfering with the host sodium-glucose co-transporter 1 (SGLT1). Our study highlights a potential novel strategy for controlling both BRV and <i>C. parvum</i> by exploiting their interactions during co-infection.