Pandemic Swine-Origin H1N1 Influenza A Virus Isolates Show Heterogeneous Virulence in Macaques

This study used virological, histological, immunological and global gene expression to compare the virlence of two newly emerged 2009 H1N1 isolates (A/Mexico/InDRE4487/2009 and A/Mexico/4108/2009) and current seasonal H1N1 influenza strain (A/Kawasaki/UTK-4/2009) in experimentally infected cynomolgus macaques. We showed that infection of macaques with two genetically similar but clinically distinct SOIV isolates from the early stage of the pandemic (A/Mexico/4108/2009 and A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections and clinical disease ranging from mild to severe pneumonia. Disease associated with these SOIV isolates was clearly advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current seasonal strain. Total dose of 7 x 10^6 pfu of influenza virus by a combination of different routes: intratracheal (4 ml), intranasal (0.5 ml each nostril), intraocular (0.5 ml each eye), and oral (1 ml).