Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

Abstract

Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-␥ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, ␥␦ T cells, dendritic cells, activated T cells, and CD4؉ and CD8 ؉ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.

Replication of influenza A virus in swine umbilical cord epithelial stem-like cells

“…Similar to these observations, we previously isolated progenitor epithelial cells from the lungs of pigs that were also surrounded by mesenchymal cells. 27 Not much is known about the exact relationship between co-existing epithelial and mesenchymal cells in this culture system. Recent publications demonstrated that MSCs can differentiate into epithelial cell phenotypes in vitro and in vivo.…”

“…Stained cells were acquired by C6 flow cytometer (BD Accuri Cytometers) and analyzed using CFlow Ò plus Software (Accuri). 27 Preparation of lung MSC-CM We collected CM from porcine lung MSCs cultures as described previously. 54 Briefly, porcine lung-MSCs were grown and expanded in DMEM containing 10% FBS.…”

“…SUCECs were infected with SwIV or HuIV at a multiplicity of infection (MOI) of 1. At indicated time points after infection, culture supernatants were collected and released virus was quantified by titration in MDCK cells 27 and expression of influenza virus nucleoprotein (NP) in infected cells at 24 h after infection was detected by IFA. 54 …”

Miniature Swine for Preclinical Modeling of Complexities of Human Disease for Translational Scientific Discovery and Accelerated Development of Therapies and Medical Devices

“…Viral mutation rates in swine have been used to inform predictive models of viral behavior affecting humans (Chang et al 2002). Swine manifest similar influenza pathogenesis as observed in humans (Khatri et al 2010) and can serve as models of immunization to aide in the understanding of individual and population (herd) immunity (Masic et al 2010;Hyland et al 2004).…”

Encephalopathy During H1N1 Influenza a Virus Infection / Encefalopatija Kod Infekcije Virusom Influence A Podtip H1N1

“…Swine flu is the name for the respiratory infection caused by influenza A virus subtype H1N1. This subtype represents the genetic combination of avian, human and swine flu (3). In contrast to the typical swine flu, this form of the virus is transmitted from human to human.…”