@article{mbs:/content/journal/jgv/10.1099/jgv.0.001075, author = "Sufiawati, Irna and Tugizov, Sharof M.", title = "HIV-induced matrix metalloproteinase-9 activation through mitogen-activated protein kinase signalling promotes HSV-1 cell-to-cell spread in oral epithelial cells", journal= "Journal of General Virology", year = "2018", volume = "99", number = "7", pages = "937-947", doi = "https://doi.org/10.1099/jgv.0.001075", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001075", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", keywords = "MAPK", keywords = "HIV", keywords = "matrix metalloproteinase-9", keywords = "NF-κB", keywords = "HSV-1", abstract = "We have shown that cell-free HIV-1 and viral proteins tat and gp120 activate mitogen-activated protein kinases (MAPKs) in tonsil epithelial cells, disrupting their tight and adherens junctions. This causes liberation of the HSV-1 receptor nectin-1 from assembled adherens junctions, leading to promotion of HSV-1 infection and spread. In the present study, we show that HIV-associated activation of MAPK leads to upregulation of transcription factor NF-κB and matrix metalloproteinase-9 (MMP-9). This induces the disruption of tight and adherens junctions, increasing HSV-1 cell-to-cell spread. Inhibition of HIV-associated MAPK activation by U0126 abolishes NF-κB and MMP-9 upregulation and reduces HSV-1 spread. Inactivation of MMP-9 also reduced HIV-promoted HSV-1 spread. These results indicate that HIV-1-activated MAPK/NF-κB and MMP-9 play a critical role in the disruption of oral epithelial junctions and HSV-1 cell-to-cell spread. Inhibition of MMP-9 expression in the oral epithelium of HIV-infected individuals may prevent the development of diseases caused by HSV-1, such as ulcers, necrotic lesions and gingivostomatitis.", }