Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung

Vidaña, Beatriz; Martínez, Jorge; Martínez-Orellana, Pamela; García Migura, Lourdes; Montoya, María; Martorell, Jaime; Majó, Natàlia

A previous study that employed the viral isolates used in this trial showed differences in the in vitro and in vivo characteristics of the two strains. In that study, the R11 strain exhibited higher in vitro replication rates between 9 and 24 hours post infection and 2 dpi in mice, and this difference was accompanied by more severe pathological lesions relative to those induced by the R61 strain [11] . As previously stated, in this study, the virulence of the R11 isolate was not consistently observed in ferrets, and more surprisingly, the R61 strain induced unexpectedly high viral titres in the lungs that were associated with severe pathological lesions in two animals. These contradictory results may be attributable to the following explanations: i) the mouse model may not be the most suitable model for assessing influenza virus pathogenicity [36] [37] [38] , and ii) ferrets, as an outbreed animal, may exhibit differential individual susceptibilities to viral infection. In humans, the genetic factors of the host are increasingly being linked to disease courses [12, 13] . Hostspecific characteristics, such as the presence of homozygous CCR5 deleterious alleles (CCR5 D 32), have been found to be associated with poor outcomes of pH1N1 infection [14] [15] [16] 20] . Interestingly, the patient from which the R11 virus was isolated was recently found to have this genotype [11] .