Abstract
The close immunological and physiological resemblance with humans makes non-human primates a valuable model for studying influenza virus pathogenesis and immunity and vaccine efficacy against infection. Although both cynomolgus and rhesus macaques are frequently used in influenza virus research, a direct comparison of susceptibility to infection and disease has not yet been performed. In the current study a head-to-head comparison was made between these species, by using a recently described swine-origin pandemic H1N1 strain, A/Mexico/InDRE4487/2009. In comparison to rhesus macaques, cynomolgus macaques developed significantly higher levels of virus replication in the upper airways and in the lungs, involving both peak level and duration of virus production, as well as higher increases in body temperature. In contrast, clinical symptoms, including respiratory distress, were more easily observed in rhesus macaques. Expression of sialyl-α-2,6-Gal saccharides, the main receptor for human influenza A viruses, was 50 to 73 times more abundant in trachea and bronchus of cynomolgus macaques relative to rhesus macaques. The study also shows that common marmosets, a New World non-human primate species, are susceptible to infection with pandemic H1N1. The study results favor the cynomolgus macaque as model for pandemic H1N1 influenza virus research because of the more uniform and high levels of virus replication, as well as temperature increases, which may be due to a more abundant expression of the main human influenza virus receptor in the trachea and bronchi.
Highlights
Animal models play an important role in studying the pathogenesis of influenza virus infections [1,2]
Using the clinical scoring system previously described by Brining et al [20], rhesus monkeys developed more clinical symptoms during the first 6 days after infection compared to cynomolgus macaques (Fig 1)
Cynomolgus and rhesus macaques are both used as animal model in influenza virus research and have been shown to be susceptible to several influenza A virus subtypes, including seasonal and pandemic H1N1, H3N2 and H5N1 [1,4,5,6,7,8,10,11,12,13,14,16,17,18]
Summary
Animal models play an important role in studying the pathogenesis of influenza virus infections [1,2]. Several macaque species, including cynomolgus macaques (Macaca fascicularis), rhesus macaques (M. mulatta) and pigtailed macaques (M. nemestrina) have been infected with human influenza A viruses [1,4,5,6,7,8,9,10,11,12,13,14]. These viruses replicate in the upper respiratory tract and infections are either asymptomatic or cause mild clinical symptoms. Acute respiratory distress and fatal outcome have been observed in these animal models after infection with avian H5N1 [4,13] and the 1918 H1N1 virus [15]
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