Domestic pigs have low susceptibility to H5N1 highly pathogenic avian influenza viruses.

Aleksandr S Lipatov,Luciana V Sarmento,Kelly M Lager,Erica Spackman,David E Swayne,Yong Kuk Kwon,David L Suarez,Richard J Webby

doi:10.1371/journal.ppat.1000102

Abstract

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.

Highlights

The genus Influenzavirus A contains individual virus strains which have infected a broad spectrum of avian and mammalian species
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
We characterized in a pig model the infection caused by four H5N1 virus strains isolated from humans, poultry and wild birds

Summary

Introduction

The genus Influenzavirus A (i.e. influenza A virus) contains individual virus strains which have infected a broad spectrum of avian and mammalian species. Most swine influenza A viruses are reassortants containing various combinations of genes originating from human, avian and swine influenza A viruses [3,4] This emphasizes that pigs are susceptible to both human and avian influenza viruses. Such susceptibility could possibly be explained by the presence of cell surface receptors for both human and avian influenza viruses on the epithelium of pig upper respiratory tract [5]. These features enable pigs to be a possible intermediate host or ‘‘mixing vessel’’, for the generation of pandemic influenza viruses through reassortment [6,7]. It is obvious that pigs are an important link in the ecology of influenza A viruses and could be a possible source of origin for human pandemic influenza

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