Domestic Pigs Have Low Susceptibility to H5N1 Highly Pathogenic Avian Influenza Viruses

Lipatov AS, Kwon YK, Sarmento LV, Lager KM, Spackm. Domestic Pigs Have Low Susceptibility to H5N1 Highly Pathogenic Avian Influenza Viruses. PLoS Pathog 4(7): e1000102. doi:10.1371/journal.pp
submited by kickingbird at Jul, 16, 2008 7:51 AM from PLoS Pathog 4(7): e1000102. doi:10.1371/journal.pp

Genetic reassortment of H5N1 highly pathogenic avian influenza viruses (HPAI) with currently circulating human influenza A strains is one possibility that could lead to efficient human-to-human transmissibility. Domestic pigs which are susceptible to infection with both human and avian influenza A viruses are one of the natural hosts where such reassortment events could occur. Virological, histological and serological features of H5N1 virus infection in pigs were characterized in this study. Two- to three-week-old domestic piglets were intranasally inoculated with 10⁶ EID₅₀ of A/Vietnam/1203/04 (VN/04), A/chicken/Indonesia/7/03 (Ck/Indo/03), A/Whooper swan/Mongolia/244/05 (WS/Mong/05), and A/Muscovy duck/Vietnam/ 209/05 (MDk/VN/05) viruses. Swine H3N2 and H1N1 viruses were studied as a positive control for swine influenza virus infection. The pathogenicity of the H5N1 HPAI viruses was also characterized in mouse and ferret animal models. Intranasal inoculation of pigs with H5N1 viruses or consumption of infected chicken meat did not result in severe disease. Mild weight loss was seen in pigs inoculated with WS/Mong/05, Ck/Indo/03 H5N1 and H1N1 swine influenza viruses. WS/Mong/05, Ck/Indo/03 and VN/04 viruses were detected in nasal swabs of inoculated pigs mainly on days 1 and 3. Titers of H5N1 viruses in nasal swabs were remarkably lower compared with those of swine influenza viruses. Replication of all four H5N1 viruses in pigs was restricted to the respiratory tract, mainly to the lungs. Titers of H5N1 viruses in the lungs were lower than those of swine viruses. WS/Mong/05 virus was isolated from trachea and tonsils, and MDk/VN/05 virus was isolated from nasal turbinate of infected pigs. Histological examination revealed mild to moderate bronchiolitis and multifocal alveolitis in the lungs of pigs infected with H5N1 viruses, while infection with swine influenza viruses resulted in severe tracheobronchitis and bronchointerstitial pneumonia. Pigs had low susceptibility to infection with H5N1 HPAI viruses. Inoculation of pigs with H5N1 viruses resulted in asymptomatic to mild symptomatic infection restricted to the respiratory tract and tonsils in contrast to mouse and ferrets animal models, where some of the viruses studied were highly pathogenic and replicated systemically.

Author Summary

Highly pathogenic avian influenza A viruses of H5N1 subtype have spread through Eurasia and Africa with continuing cases of human infection, suggesting the potential to become a pandemic influenza virus. Pigs which are susceptible to infection with both human and avian influenza A viruses are one of the natural hosts where a pandemic virus could be produced. In this study, we characterized in a pig model the infection caused by four H5N1 virus strains isolated from humans, poultry and wild birds. We demonstrated that exposure of pigs through the nose with H5N1 viruses or consumption of meat from infected chickens resulted in infection with mild weight loss. In contrast to mouse and ferret animal models where some of viruses were highly pathogenic and replicated in multiple organs, replication of H5N1 viruses in pigs was restricted to the respiratory tract, mainly to the lungs, and tonsils. Mild to moderate bronchiolitis and pneumonia were observed in the lungs of infected animals. Our results demonstrated that domestic pigs had low susceptibility to infection and disease with highly pathogenic H5N1 influenza A viruses.