Immunity & infection

Poster

Dendritic Cells Challenged with an Glycoprotein D-deficient Herpes Simplex Virus Type 2 Activate cd4+ and cd8+ T Cells

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

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are prevalent in the human population and produce lifelong infections with frequent reactivations. Persistence in the host relies, within others on the evasion of innate and adaptive immunity and may result in pathology. Noteworthy, HSV interfere with the maturation and viability of dendritic cells (DCs), likely affecting the capacity of the host to mount effective adaptive immune responses against these viruses. An HSV-2 mutant that has the US6 gene deleted (encoding glycoprotein D, gD) and is phenotypically complemented with the gD protein on its surface, was previously reported to be safe, immunogenic and induce protective immunity against skin and genital challenges with HSV-1 and HSV-2 in animals (eLife;4:e06054,2015, doi: http://dx.doi.org/10.7554/eLife.06054). Here, we sought to evaluate whether this HSV-2 gD-mutant was attenuated in murine DCs and whether it was able to license these cells to activate T cells. We observed that, unlike wild-type (WT) HSV-2 and other glycoprotein-mutant viruses, the gD-deletant was innocuous to DCs and promoted both, their maturation and capacity to activate naïve CD8+ and CD4+ T cells. Furthermore, DCs exposed to the WT and gD-mutant virus experienced different unfolded protein responses. Taken together, these results suggest that the attenuated phenotype of the gD-mutant virus in DCs is particular to this virus and likely accounts for its significant immunogenicity in vivo, as well its vaccine-like properties. Assessing the virulence of HSV mutants in DCs may provide grounds for identifying novel attenuated viruses that are protective in vivo.

Angello Retamal-Diaz

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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    Eduardo Tognarelli

    Ungraduated 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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      Diana C.M. Alvarez

      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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