Viral Sepsis in Children

Gupta, Neha; Richter, Robert; Robert, Stephen; Kong, Michele

avian influenza have been shown to upregulate production and release of tumor necrosis factor (TNF)-related apoptosisinducing ligand (TRAIL) that promote T-cell apoptosis (67) . Though the effect of TRAIL on other cell lineages was not determined, it is plausible that the effect seen in T-cells may be more diffuse. Systemic viral dissemination from sites of primary infection (e.g., human metapneumovirus in the respiratory tract or HPeV in the gastrointestinal tract) may occur through these apoptotic mechanisms, whereby new virions are released, infect local endothelial cells, and cause further cellular apoptosis and systemic viral spread. The invasiveness and pervasiveness of the viral infection is likely dictated by cell tropism and genetically determined virulence as viruses with greater cytopathogenicity, such as H5N1 avian influenza (66) and HPeV-3 (68) , are more likely to cause sepsis in immunocompetent hosts than viruses with typically minimal associated cytopathology (e.g., RSV or parainfluenza) (69) . Lastly, effectors of the host immune system, such as natural killer (NK), cytotoxic CD8+ T cells and complement, attack, and destroy virally infected host cells.