Open AccessEarly activation of MyD88-mediated autophagy sustains HSV-1 replication in human monocytic THP-1 cells
Author(s) -
Gabriel Siracusano,
Assunta Venuti,
Daniele Lombardo,
Antonio Mastino,
Audrey Esclatine,
Maria Teresa Sciortino
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep31302
Subject(s) - autophagy , thp1 cell line , microbiology and biotechnology , biology , tlr2 , innate immune system , viral replication , gene knockdown , signal transduction , cell culture , virus , receptor , virology , genetics , tlr4 , apoptosis
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.