NSP4 (rotavirus) explained

The rotavirus nonstructural protein NSP4 was the first viral enterotoxin discovered.^[1] It is a viroporin^[2] and induces diarrhea and causes Ca²⁺-dependent transepithelial secretion.^[3]

A transmembrane glycoprotein, NSP4 is organized into three main domains: a three-helical TM domain in the N-terminus (also a viroporin domain), a central cytoplasmic coiled-coil domain for multimerization, and a C-terminal flexible region. It can also be secreted out of the cell. As of 2019, only structures of the central domain, which is responsible for diarrhea, has been solved. It oligomerizes into dimeric, tetrameric, pentameric, and even higher-order forms.^[4]

Notes and References

1. Dong Y, Zeng CQ, Ball JM, Estes MK, Morris AP . The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production . Proceedings of the National Academy of Sciences of the United States of America . 94 . 8 . 3960–5 . April 1997 . 9108087 . 20550 . 10.1073/pnas.94.8.3960 . 1997PNAS...94.3960D . free .
2. Pham T, Perry JL, Dosey TL, Delcour AH, Hyser JM . The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel . Scientific Reports . 7 . 43487 . March 2017 . 28256607 . 5335360 . 10.1038/srep43487 . 2017NatSR...743487P .
3. Gebert JT, Hyser J . Using Forward and Reverse Genetics to Understand Calcium Dysregulation in Enteric Viral Virulence . FASEB Journal . 36 . Suppl 1. May 2022 . 35557094 . 10.1096/fasebj.2022.36.S1.R3214 . free . 248633853 .
4. Hu L, Crawford SE, Hyser JM, Estes MK, Prasad BV . Rotavirus non-structural proteins: structure and function . Current Opinion in Virology . 2 . 4 . 380–8 . August 2012 . 22789743 . 3422752 . 10.1016/j.coviro.2012.06.003 .