Tuesday, December 16, 2014

Prevention and Cure of Rotavirus Infection

Rotavirus (RV) is an RNA virus that causes diarrhea leading to severe dehydration in children and moderate intestinal discomfort in adults.  Mice have proven to be a useful animal model in studying infection of RV – the findings in mice are consistent with what is found in regards to human infection as well.  In this model, it has been shown that the level of infection of this virus can be ascertained by the appearance of the appropriate viral antigens in feces.    It has also been shown that the typical target for RV is the epithelial cells that line the small intestine.  

Furthermore, it seems that the predominant antigen that activates host cell gene expression as a defense against infection in intestinal epithelial cells (IECs) is the protein flagellin – a major component of bacterial flagella.  Flagellin seems to be the dominant activator of the immune system in the intestine.   It has been shown that flagellin-activated responses protect mice against bacterial infection, chemical insult and radiation.  In addition, administration of flagellin to mice seems to reduce the likelihood of infection with a cultured and attenuated form of RV.

Benyue Zhang and his colleagues at the Center of Inflammation, Immunity and Infection at the Institute of Biomedical Sciences Georgia State University, Atlanta Georgia, sought to discover if the administration of flagellin could serve as a prophylactic to protect mice from a highly contagious and pathogenic mouse RV strain.

The result of this study was very encouraging since the data demonstrated that not only did the administration of flagellin to mice prevent the onset of RV infection, but also cured infected mice who suffered from a chronic infection of the virus.  Interestingly, their findings have shown that this protective effect was not dependent upon adaptive immunological responses nor did the underlying mechanism require the participation of Interferon (IFN) – a substance known for its potent anti-viral properties.
The data did show, however, that the flagellin-initiated response required Toll-like receptor 5 (TLR5) and the involvement of Dendritic cells that produce interleukin-22 (IL-22).  Interleukins are members of a family of cytokines that play an essential role in immune responses.  The net result of these processes is the expression of a so-called “protective gene expression program” within intestinal epithelial cells.

These results may have public health implications in regards to rotavirus infections within the human population.   This is of particular importance since it is estimated that RV infections result in the deaths of approximately 600,000 children annually throughout the world.    

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