Comparative Pathogenicity Of Swine-and Human-Origin2009/H1N1Influenza Virus

Since the emergence of the pandemic (H1N1)2009virus (2009/H1N1) in April2009, the cases of transmission from humans to pigs have been reported frequently. To better understand the comparative pathogenesis of the novel strains isolated from pigs and the human isolate, we inoculated mice intranasally with the viruses, and monitored their morbidity, mortality, viral replication, cytokine production and lung histology. Results showed that pig isolates replicated efficiently in the lungs and could even cause lethal disease. Cytokines expression analysis indicated that mice challenged with the lethal strains could induce higher production of cytokines than other viruses at the early stage. Further more, the novel isolates belonged to the clade7sublineage of2009/H1N1viruses, of which six common mutations were found among the viral proteins:HA:E103D, P145S;NS1:V123I;PB2:I588T;PA:V70A,E547D.indicating a possible correlation between molecular factors and virus pathogenicity. These studies demonstrate that the pig isolates exhibited enhanced pathogenicity in mice compared with human isolates.Given that the four2009/H1N1influenza virus were isolated from pigs, we chose a classic swine influenza virus (SIV) as a reference, to compare the pathogenicity in mice, virus replication in PAM cell and cytokine expression. The results showed that p-H1N1can significantly induce the body weight loss of mice significantly and replicate more effectively in PAM than SIV. At3h and6h post infection, most inflammatory factors cytokines including interleukins didn’t display significant differences in the PAM between these two viruses. Furthermore, at12h and24h post infection, cytokines induced by SIV were higher than that of p-H1N1except IL-29. However, at6h post infection, p-H1N1virus can induce a larger number of productions of interferon IL-29than that of SIV. At12h and24h post infection, SIV was able to lead to higher expression of IL-29.