Ocular infection of mice with influenza A (H7) viruses: A site of primary virus replication and spread to the respiratory tract.

Session IV: Belser

Title of Contribution: Ocular infection of mice with influenza A (H7) viruses: A site of primary virus replication and spread to the respiratory tract.

Author(s): Jessica A. Belser1,2, Debra A. Wadford1, Jacqueline M. Katz1, and Terrence M. Tumpey1

Affiliation(s): 1Immunology and Pathogenesis Branch, Influenza Division, CCID, CDC, Atlanta, Georgia; 2Department of Microbiology, Mount Sinai School of Medicine, New York City, New York

Abstract:

Avian H7 influenza viruses have been responsible for poultry outbreaks worldwide and have resulted in numerous cases of human infection in recent years. The majority of human infections associated with H7 influenza viruses have resulted in ocular infection, which may represent a portal of entry for influenza viruses. The high rate of conjunctivitis in workers exposed to H7N7-infected poultry during an outbreak response in the Netherlands in 2003 highlights the need to better understand this additional route of virus entry. To investigate the apparent ocular tropism observed in humans following infection with H7 influenza viruses, mice were inoculated by the ocular route with viruses of multiple subtypes and degrees of virulence. We found that H7N7 viruses isolated from the Netherlands in 2003 and H7N3 viruses isolated from British Columbia, Canada in 2004, two subtypes that were highly virulent for poultry, replicated to significant titer in the mouse eye. In contrast, human (H3N2 and H1N1) or avian influenza H5N1 subtype viruses did not replicate to significant titer in the eye following ocular inoculation. Remarkably, some H7N7 and H5N1 viruses spread systemically following ocular inoculation, including to the brain, resulting in morbidity and mortality of mice. Highly pathogenic avian influenza viruses of both H7 and H5 subtypes replicated efficiently in murine corneal epithelial sheets and human corneal epithelial cells, whereas human influenza subtype viruses did not. Sialic acid binding specificity did not predict the ability of avian or human viruses to bind ocular tissue. These findings demonstrate that avian influenza viruses within multiple subtypes are capable of using the eye as a portal of entry.