Kinetics of viral replication and induction of host responses in ferrets differs between ocular and intranasal routes of inoculation

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Virology (Impact Factor: 3.32). 02/2013; 438(2). DOI: 10.1016/j.virol.2013.01.012
Source: PubMed


While influenza viruses are typically considered respiratory pathogens, the ocular system represents a secondary entry point for virus to establish a productive respiratory infection and the location for rare instances of virus-induced conjunctivitis. We used the ferret model to conduct a side-by-side comparison of virus infectivity, kinetics of viral replication, and induction of host responses following inoculation by either the intranasal or ocular routes with two viruses, A/Netherlands/230/03 (H7N7) and A/Panama/2007/99 (H3N2). We show that ocular inoculation resulted in delayed virus replication and reduced levels of proinflammatory cytokine and chemokine transcript in respiratory tract but not ocular tissues compared with intranasally inoculated animals. We identified numerous proinflammatory mediators with known roles in ocular disease elicited in ferret eye tissue following influenza virus infection. These findings provide a greater understanding of the modulation of host responses following different inoculation routes and underscore the risk associated with ocular exposure to influenza viruses.

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    • "Expression of cytokine and chemokine genes has been assessed in ex vivo samples following infection of naïve or vaccinated ferrets with influenza virus or SARS-CoV by microarray analysis (Cameron et al., 2008; Fang et al., 2010; Rowe et al., 2010). Cytokine and chemokine gene profiles have also been assessed ex vivo and in in vitro epithelial cultures using SYBR green real time RT-PCR assays (Svitek and von Messling, 2007; Cameron et al., 2008; Danesh et al., 2008, 2011; Svitek et al., 2008; Kim et al., 2009; Fang et al., 2010; Hamelin et al., 2010; Kobinger et al., 2010; Rowe et al., 2010; Kang et al., 2011; Meunier and von Messling, 2011, 2012; Pillet et al., 2011; Huang et al., 2012; Maines et al., 2012; Meunier et al., 2012; Belser et al., 2013; Zeng et al., 2013). TaqMan chemistry incorporates target-specific fluorescent labeled probes enabling multiple genes can be assessed in a single real time PCR reaction (Giulietti et al., 2001). "
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