Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses

• Published in: Nature communications Vol. 14; no. 1; p. 1456
• Main Authors: Deng, Silu, He, Wei, Gong, Ai-Yu, Li, Min, Wang, Yang, Xia, Zijie, Zhang, Xin-Tiang, Huang Pacheco, Andrew S., Naqib, Ankur, Jenkins, Mark, Swanson, Patrick C., Drescher, Kristen M., Strauss-Soukup, Juliane K., Belshan, Michael, Chen, Xian-Ming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-03-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 13/51; 14/63; 38/39; 38/77; 38/89; 38/90; 38/91; 631/250/255/1715; 631/326/417/2546; 692/420/254; Animals; Antiparasitic agents; Antiparasitic Agents - metabolism; Antiparasitic Agents - pharmacology; Cryptosporidiosis - etiology; Cryptosporidiosis - parasitology; Cryptosporidiosis - virology; Cryptosporidium; Cryptosporidium - pathogenicity; Cryptosporidium - virology; Cryptosporidium parvum; Cryptosporidium parvum - pathogenicity; Cryptosporidium parvum - virology; Diarrhea; Double Stranded RNA Viruses - metabolism; Double-stranded RNA; Epithelial cells; Epithelium; Host-Parasite Interactions - genetics; Humanities and Social Sciences; Infections; Interferon; Interferon Type I - metabolism; Interferon Type I - pharmacology; Intestine; Mice; multidisciplinary; Parasites; Protozoa; RNA viruses; Science; Science (multidisciplinary); Signaling; Viruses; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-37129-0

Cryptosporidium
infects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure.
Cryptosporidium parvum
virus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored by
Cryptosporidium
spp. Here we show that intestinal epithelial conditional
Ifnar1
−/−
mice (deficient in type I IFN receptor) are resistant to
C. parvum
infection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. Whereas
C. parvum
infection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-
C. parvum
defense and
Cryptosporidium
uses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response.
Cryptosporidium parvum
virus 1 is a virus harbored by the pathogenic protozoan
Cryptosporidium parvum
, and whose role in parasite biology and host interactions remains unclear. Here, Deng
et al
. demonstrate the impact this virus has on host response and infection outcome.