Ocular tropism of respiratory viruses.

Address correspondence to Jessica A. Belser, .
Microbiology and molecular biology reviews: MMBR (Impact Factor: 15.26). 03/2013; 77(1):144-56. DOI: 10.1128/MMBR.00058-12
Source: PubMed

ABSTRACT SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT The ongoing H7N9 influenza epizootic in China once again presents us questions about the origin of pandemics and how to recognize them in early stages of development. Over the past ~135 years, H7 influenza viruses have neither caused pandemics nor been recognized as having undergone human adaptation. Yet several unusual properties of these viruses, including their poultry epizootic potential, mammalian adaptation, and atypical clinical syndromes in rarely infected humans, suggest that they may be different from other avian influenza viruses, thus questioning any assurance that the likelihood of human adaptation is low. At the same time, the H7N9 epizootic provides an opportunity to learn more about the mammalian/human adaptational capabilities of avian influenza viruses and challenges us to integrate virologic and public health research and surveillance at the animal-human interface.
    mBio 06/2013; 4(4). DOI:10.1128/mBio.00445-13 · 6.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The study of respiratory pathogens has traditionally been performed by examining virus exposure to and infection of respiratory tract tissues. However, these studies typically overlook the role of ocular surfaces, which represent both a potential site of virus replication and a portal of entry for the establishment of a respiratory infection. To model transocular virus entry in a mammalian species, we established a novel inoculation method that delivers an aerosol inoculum exclusively to the ferret ocular surface. Using influenza as a representative respiratory pathogen, we found that both human and avian viruses mounted a productive respiratory infection in ferrets following ocular-only aerosol inoculation, and demonstrated that H5N1 exposure can result in a fatal infection at viral doses below 10 PFU or for as little as 2 minutes of virus exposure. Ferrets inoculated by the ocular aerosol route with avian (H7N7, H7N9) or human (H1N1, H3N2v) viruses were capable of transmitting virus to naïve animals in direct contact or respiratory droplet models, respectively. Our results reveal that ocular-only exposure to virus-containing aerosols constitutes a valid exposure route for a potentially fatal respiratory infection, even among viruses which do not demonstrate an ocular tropism, underscoring the public health implications of ocular exposure in clinical or occupational health settings.
    Journal of Virology 06/2014; 88(17). DOI:10.1128/JVI.01067-14 · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Defective interfering (DI) RNAs are highly deleted forms of the infectious genome that are made by most families of RNA viruses. DI RNAs retain replication and packaging signals, are synthesized preferentially over infectious genomes, and are packaged as DI virus particles which can be transmitted to susceptible cells. Their ability to interfere with the replication of infectious virus in cell culture, and their potential as antivirals in the clinic has long been known. However, up to now, no realistic formulation has been described. In this review, we consider the early evidence of antiviral activity by DI viruses and, using the example of DI influenza A virus, and outline developments that have led to the production of a cloned DI RNA that is highly active in preclinical studies not only against different subtypes of influenza A virus but also against heterologous respiratory viruses. These data suggest that it is timely to reassess the potential of DI viruses as a novel class of antivirals that may have general applicability.
    Journal of Virology 02/2014; 88(10). DOI:10.1128/JVI.03193-13 · 4.65 Impact Factor


Available from