A Herpes Simplex Virus Type 2 Deleted for Glycoprotein D Enables Dendritic Cells to Activate CD4+ and CD8+ T Cells

Abstract : Herpes simplex virus type 2 (HSV-2) is highly prevalent in the human population producing significant morbidity, mainly because of the generation of genital ulcers and neonatal encephalitis. Additionally, HSV-2 infection significantly increases the susceptibility of the host to acquire HIV and promotes the shedding of the latter in the coinfected. Despite numerous efforts to create a vaccine against HSV-2, no licensed vaccines are currently available. A long-standing strategy, based on few viral glycoproteins combined with adjuvants, recently displayed poor results in a Phase III clinical study fueling exploration on the development of mutant HSV viruses that are attenuated in vivo and elicit protective adaptive immune components, such as antiviral antibodies and T cells. Importantly, such specialized antiviral immune components are likely induced and modulated by dendritic cells, professional antigen presenting cells that process viral antigens and present them to T cells. However, HSV interferes with several functions of DCs and ultimately induces their death. Here, we propose that for an attenuated mutant virus to confer protective immunity against HSV in vivo based on adaptive immune components, such virus should also be attenuated in dendritic cells to promote a robust and effective antiviral response. We provide a background framework for this idea, considerations, as well as the means to assess this hypothesis. Addressing this hypothesis may provide valuable insights for the development of novel, safe, and effective vaccines against herpes simplex viruses.
Document type :
Journal articles
Complete list of metadatas

Cited literature [112 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02153635
Contributor : Ana Paula Dutra Azevedo <>
Submitted on : Wednesday, June 12, 2019 - 1:31:43 PM
Last modification on : Tuesday, August 13, 2019 - 2:30:12 PM

File

fimmu-08-00904.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Angello Retamal-Díaz, Alexis Kalergis, Susan Bueno, Pablo González. A Herpes Simplex Virus Type 2 Deleted for Glycoprotein D Enables Dendritic Cells to Activate CD4+ and CD8+ T Cells. Frontiers in Immunology, Frontiers, 2017, 8, ⟨10.3389/fimmu.2017.00904⟩. ⟨inserm-02153635⟩

Share

Metrics

Record views

55

Files downloads

86