Immunity & infection

Poster

Pharmacological Induction of Heme oxygenase-1 Activity Blocks Herpes Simplex Virus Infection

Wednesday, June 14
6:15 PM - 7:45 PM

Heme oxygenase-1 (HO-1) is a host inducible enzyme that responds to numerous stress-related stimuli, such as reactive oxygen species, hyperthermia, UV radiation and infections. HO-1 degrades iron-containing heme into ferrous iron (Fe2+), carbon monoxide (CO) and biliverdin. Noteworthy, these products elicit cytoprotective events that limit damaging oxidation within cells, as well as apoptosis. Moreover, recent studies reveal that HO-1 products also exhibit antiviral effects against several viruses such as Ebola, influenza and hepatitis C, among others. Here, we sought to assess the role of HO-1 over herpes simplex virus (HSV) infection in vitro, by pharmacologically modulating the activity of HO-1. Importantly, we found that inducing HO-1 activity with cobalt protoporphyrin (CoPP) significantly decreased HSV replication in human epithelial cells and neurons, even though equivalent amounts of virus bound to the surface of CoPP- and vehicle-treated cells and a similar quantity of virus entered the cytoplasm early after infection. Concomitant with reduced virus output, we observed decreased expression of HSV-encoded genes in CoPP-treated cells, as compared to untreated cells or cells treated with SnPP, an inhibitor of HO-1 activity. Remarkably, CoPP-treatment hampered viral capsid accumulation around the nucleus in HSV-infected cells, suggesting that HO-1 activity likely blocks viral genome delivery into the nucleus of virus-inoculated cells. These findings extend the antiviral effects of HO-1 onto HSV and suggest a novel strategy for treating infection with this type of viruses. 

Francisco J. Ibáñez

PhD student
Departamento de Genética Molecular y Microbiología, Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile.

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    Monica A. Farías

    Undergraduate Student, Biochemistry
    Departamento de Genética Molecular y Microbiología, Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile.

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      Janyra Espinoza

      PhD Student
      Departamento de Genética Molecular y Microbiología, Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile.

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        Alexis M. M. Kalergis

        Titular professor
        Millennium Institute of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile

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          Pablo A. Gonzalez

          Assistant professor
          Departamento de Genética Molecular y Microbiología, Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile.

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