Do viral infections mimic bacterial sepsis? The role of microvascular permeability: A review of mechanisms and methods

Abstract

A dysregulated immune response and functional immunosuppression have been considered the major mechanisms of the bacterial sepsis syndrome. More recently, the loss of endothelial barrier function and resultant microvascular leak have been found to be a key determinant of the pathogenesis of bacterial sepsis. Whether a similar paradigm applies to systemic viral syndromes is not known. Answering this question has far-reaching implications for the development of future anti-viral therapeutic strategies. In this review, we provide an overview of the structure and function of the endothelium and how its barrier integrity is compromised in bacterial sepsis. The various in vitro and in vivo methodologies available to investigate vascular leak are reviewed. Emphasis is placed on the advantages and limitations of cell culture techniques, which represent the most commonly used methods. Within this context, we appraise recent studies of three viruses - hantavirus, human herpes virus 8 and dengue virus - that suggest microvascular leak may play a role in the pathogenesis of these viral infections. We conclude with a discussion of how endothelial barrier breakdown may occur in other viral infections such as H5N1 avian influenza virus.