Pathogenesis of Pandemic H1N1

Abstract

The pandemic influenza A H1N1 (pdm H1N1) emerged in California and Mexico in April 2009. There was initial fear that the case fatality rate (CFR) could be 2% as reported in Mexico, but now it is clear that the pdm H1N1 causes a disease no more severe than seasonal influenza with a CFR between 0.1 to 0.2%. However it could cause serious morbidities and deaths in pregnant women, obese persons and patients with chronic underlying disease. Early animal studies using ferrets, mice and macaques of pdm H1N1 infection suggest more severe illness compared with seasonal influenza, although much less virulent than H5N1 or the 1918 pdm Spanish flu virus. However later studies using human immune cells and respiratory epithelial tissues ex vivo suggest similar capacity of pdm H1N1 for cytokine induction as seasonal influenza virus, but differs in its ability to replicate in human conjunctiva. Post-mortem studies of patients died from pdm H1N1 revealed tracheitis, bronchiolitis and diffuse alveolar damage. Viral antigen was seen most commonly in the epithelium of tracheobronchial tree. Marked expression of TLR-3 and IFN-γ, with CD8+T cells and granzme B+ cells were noted in the lung, with no evidence of viral dissemination outside the lung. Evidence of secondary bacterial superinfection with Streptococcus pneumoniae and Staphylococcus aureus was common. Susceptibility to pdm H1N1 is less in elderlies over 65 years old than the younger population because of their higher prevalence of cross-reacting antibodies. The overall mild disease severity of pdm H1N1 influenza may be related to pre-existing T-cell memory due to the conservation of a large fraction of T-cell epitopes between seasonal influenza and pdm H1N1. There is also some evidence to suggest people deficient in IgG2 may be more susceptible to pdm H1N1.We are interested in defining cross-reacting T cell responses as well as the role of mannose binding lectin in pdm H1N1.