Anti-Inflammatory Proteins to treat Viral Sepsis

Viral sepsis is a preventable cause of morbidity and mortality for the United States military. Sepsis is caused by a dysregulation of the host response to a pathogen. One third of those who develop sepsis die. One factor often overlooked in our response to sepsis is that the diseases they have striking similarities. Our proposal focuses on the similarities in the inflammation associated with sepsis to rapidly target the symptoms by using anti-inflammatory viral proteins encoded by poxviruses to controlling sepsis induced inflammation. To date we have shown that the administration of the poxvirus protein chemokine response modifier D (CrmD) during severe dengue in our mouse model prolongs survival. This result is significant as it suggests that administration of CrmD can increase the time to diagnosis and treat disease which can save lives. We have also shown that the vaccinia virus complement control protein (VCP) can reduce compliment activation caused by severe dengue in our model. This results is significant as it demonstrates that the administration of VCP can block complement activation which is though to be a major contributor of inflammation.