While we are unable to determine which isoforms are being elicited by virus infection due to a lack of isoform-specific antibodies, the fact that blocking TLR4 signaling with Eritoran inhibits HMGB1 release into serum in virus-infected mice and cotton rats and the fact that the HMGB1 antagonist P5779 also binds to the TLR4 MD-2 coreceptor would suggest that it is the disulfide isoform that is active in our system (14, 15). The gene discussed is HMGB1; the disease is viral infectious disease.