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

**Authors:** Fumi Murakoshi, Megumi Itoh, Rofaida Mostafa Soliman, Tatsunori Masatani, Kenichi Shibano, Takaaki Nakaya, Kentaro Kato

PMC · DOI: 10.3389/fvets.2026.1715161 · Frontiers in Veterinary Science · 2026-02-17

## TL;DR

This study explores how co-infection with rotavirus and Cryptosporidium affects disease severity in calves and suggests a potential new approach for controlling these infections.

## Contribution

The study reveals that bovine rotavirus can reduce the severity of Cryptosporidium infection in calves, offering a novel strategy for disease control.

## Key findings

- Subclinical rotavirus infection shortened the duration of Cryptosporidium-induced diarrhea in calves.
- Bovine rotavirus NSP4 protein inhibits Cryptosporidium parvum infection in vitro, possibly via interference with SGLT1.

## Abstract

Rotavirus A (RVA; species Rotavirus alphagastroenteritidis) and Cryptosporidium 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 Cryptosporidium. 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 Cryptosporidium 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 Cryptosporidium parvum in calves and reduced initial oocyst shedding. Furthermore, in vitro experiments using the bovine intestinal epitheliocyte (BIE) cell line demonstrated that the BRV Lincoln strain (G6, P[1]) non-structural protein 4 (NSP4) inhibits C. parvum 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 C. parvum by exploiting their interactions during co-infection.

## Linked entities

- **Proteins:** PRSS57 (serine protease 57), SLC5A1 (solute carrier family 5 member 1)
- **Diseases:** diarrhea (MONDO:0001673), rotavirus infection (MONDO:0005194)
- **Species:** Bos taurus (taxon 9913), Cryptosporidium parvum (taxon 5807), Rotavirus alphagastroenteritidis (taxon 3432193)

## Full-text entities

- **Genes:** IL10 (interleukin 10) [NCBI Gene 281246] {aka IF2A}, IFNA16 (interferon, alpha 16) [NCBI Gene 510726] {aka IFN}, IFNG (interferon gamma) [NCBI Gene 281237], SLC5A1 (solute carrier family 5 member 1) [NCBI Gene 282361] {aka SGLT1}
- **Diseases:** enteric co-infections (MESH:D004751), fungal (MESH:D009181), Rotavirus (MESH:D012400), watery diarrhea (MESH:D003969), Calf D (MESH:D048089), Cryptosporidiosis (MESH:D003457), Diarrheal diseases (MESH:D004403), viral infection (MESH:D014777), -infection (MESH:D007239), Cytotoxicity (MESH:D064420), Diarrhea (MESH:D003967), acute diarrhea (MESH:D000208), intestinal inflammation (MESH:D007249), growth retardation (MESH:D006130), acute gastroenteritis (MESH:D005759)
- **Chemicals:** Phlorizin (MESH:D010695), sucrose (MESH:D013395), glucose (MESH:D005947), 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino) (-), 2NBDG (MESH:C000724151), 2-NBDG (MESH:C098340), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), sodium (MESH:D012964), penicillin (MESH:D010406), nitazoxanide (MESH:C041747), MTT (MESH:C070243), Cl- (MESH:D002713), halofuginone lactate (MESH:C010176), sodium taurocholate (MESH:D013656), Alexa Fluor 555 (MESH:C000608607), methanol (MESH:D000432), Poly(I:C) (MESH:D011070), N (MESH:D009584), cesium chloride (MESH:C028019), streptomycin (MESH:D013307)
- **Species:** Cryptosporidium parvum virus 1 (no rank) [taxon 675060], Rotavirus A (no rank) [taxon 28875], Bos taurus (bovine, species) [taxon 9913], Bovine rotavirus (no rank) [taxon 10927], Cryptosporidium parvum (species) [taxon 5807], Chlorocebus aethiops (African green monkey, species) [taxon 9534], Homo sapiens (human, species) [taxon 9606], Salmonella enterica (species) [taxon 28901], Gammacoronavirus (genus) [taxon 694013], Bovine rotavirus A (no rank) [taxon 35333], Clostridium perfringens (species) [taxon 1502], Escherichia coli (E. coli, species) [taxon 562], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** BIE — Bos taurus (Bovine), Transformed cell line (CVCL_HC67), 17 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_8991), MA104 — Chlorocebus pygerythrus (Vervet monkey), Spontaneously immortalized cell line (CVCL_3845), HNJ-1 — Mus musculus (Mouse), Hybridoma (CVCL_C7RB)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12953082/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12953082/full.md

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Source: https://tomesphere.com/paper/PMC12953082