Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 56
Hantavirus infection of lung microvascular endothelial cells activates the extracellular
regulated kinase 1 /2 (ERK1/2) and phosphoinositol3-kinase (PI3K) pathways leading to
proinflammatory cytokine/chemokine production.
Christina F. Spiropoulou, Karen L. Hutchinson, Cesar Albarino, Thomas G. Ksiazek
and Pierre E. Rollin
Special Pathogens Branch, Division of Viral and Rickettsial Diseases, Centers for
Disease Control and Prevention, Atlanta, GA 30333, USA. E-mail:ccs8@cdc.gov
Hantavirus pulmonary syndrome (HPS), is a severe respiratory illness with approximately
40% mortality which is caused by New World hantaviruses. In humans, the primary target
organ for virus infection is the lung, and severe disease symptoms have been attributed to
massive lung endothelial cell capillary leakage. Immunopathology studies have shown the
presence of monocytic and lymphocytic cell infiltrates in the microvasculature of patients but
no evidence of endothelial cell disruption. Hantavirus infection of primary microvascular
endothelial cells in vitro also does not cause cell disruption but induces the upregulation of a
number of proinflammatory chemokines. These observations have led to the hypothesis that
host immune responses play a crucial role in the pathogenesis of hantavirus diseases. This
study was designed to examine pathways participating in the induction of proinflammatory
chemokines by hantavirus infection. Hantavirus entry and replication activates the
extracellular regulated kinase 1 /2 (ERK1/2) and phosphoinositol3-kinase (PI3K) pathways.
By using specific pharmacological inhibitors we have shown that both pathways contribute to
the induction of proinflammatory cytokines/chemokines by hantaviruses. However, we
observed a partial inhibition using inhibitors specific for the ERK1/2 pathway whereas total
inhibition of virus induced cytokines and chemokines was seen with LY294002, an inhibitor
of PI3K. Studies leading to discovery of possible pharmacotherapeutic interventions for HPS
are important given the lack of effective hantavirus vaccines.
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