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.
