Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. May 12, 2016; 5(2): 38-62
Published online May 12, 2016. doi: 10.5501/wjv.v5.i2.38
Inflammatory and oxidative stress in rotavirus infection
Carlos A Guerrero, Orlando Acosta
Carlos A Guerrero, Orlando Acosta, Department of Physiological Sciences, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá 111311, Colombia
Author contributions: Both authors contributed equally to critically reading, analyzing and writing the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Carlos A Guerrero, MD, MSc, PhD, Professor of Medicine, Department of Physiological Sciences, Faculty of Medicine, Universidad Nacional de Colombia, Carrera 45 # 26-85, Bogotá 111311, Colombia.
Telephone: +57-1-3165000 Fax: +57-1-3165000
Received: August 12, 2015
Peer-review started: August 13, 2015
First decision: September 28, 2015
Revised: December 2, 2015
Accepted: January 27, 2016
Article in press: January 29, 2016
Published online: May 12, 2016

Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virus-associated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines.

Keywords: Rotaviruses, Oxidative stress, Inflammatory signaling, Antioxidant treatment, Anti-inflammatory treatment

Core tip: Rotavirus entry into the host cell requires cell surface molecules providing binding, chaperoning and oxido-reducing functions. Sialic acid/integrin α2β1, heat shock cognate protein 70 and protein disulfide isomerase (PDI) seem to perform these functions. Recently, the cell surface oxido-reduction activity based at least on PDI has been highlighted as a potential determinant of the conformational changes that are required by viral structural proteins in order to facilitate virus entry. The rotavirus-induced oxidative stress and inflammatory signaling is an attractive target for therapeutic intervention as antioxidant and anti-inflammatory treatment has proved to efficiently inhibit rotavirus infection.