title: Early activation of MyD88-mediated autophagy sustains HSV-1 replication in human monocytic THP-1 cells.
abstract: Autophagy is a cellular degradation pathway that exerts numerous functions in vital biological processes. Among these, it contributes to both innate and adaptive immunity. On the other hand, pathogens have evolved strategies to manipulate autophagy for their own advantage. By monitoring autophagic markers, we showed that HSV-1 transiently induced autophagosome formation during early times of the infection of monocytic THP-1 cells and human monocytes. Autophagy is induced in THP-1 cells by a mechanism independent of viral gene expression or viral DNA accumulation. We found that the MyD88 signaling pathway is required for HSV-1-mediated autophagy, and it is linked to the toll-like receptor 2 (TLR2). Interestingly, autophagy inhibition by pharmacological modulators or siRNA knockdown impaired viral replication in both THP-1 cells and human monocytes, suggest that the virus exploits the autophagic machinery to its own benefit in these cells. Taken together, these findings indicate that the early autophagic response induced by HSV-1 exerts a proviral role, improving viral production in a semi-permissive model such as THP-1 cells and human monocytes.
authors: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.
authors: Gabriel
authors: G
authors: Siracusano
authors: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20127 Milan, Italy.
authors: Assunta
authors: A
authors: Venuti
authors: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.
authors: Daniele
authors: D
authors: Lombardo
authors: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.|The Institute of Translational Pharmacology, CNR, Via Fosso del Cavaliere 100, I-00133, Rome, Italy.
authors: Antonio
authors: A
authors: Mastino
authors: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France.
authors: Audrey
authors: A
authors: Esclatine
authors: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.
authors: Maria Teresa
authors: MT
authors: Sciortino
mesh_terms: D056704:Adaptive Immunity; D001343:Autophagy; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015398:Signal Transduction; D000074084:THP-1 Cells; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2