1887

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Volume 99, Issue 7

HIV-induced matrix metalloproteinase-9 activation through mitogen-activated protein kinase signalling promotes HSV-1 cell-to-cell spread in oral epithelial cells Open Access

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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): HIV , HSV-1 , MAPK , matrix metalloproteinase-9 and NF-κB
© 2018 The Authors
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2018-07-01
2023-05-29
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HIV-induced matrix metalloproteinase-9 activation through mitogen-activated protein kinase signalling promotes HSV-1 cell-to-cell spread in oral epithelial cells
J. Gen. Virol. 99, 937 (2018); https://doi.org/10.1099/jgv.0.001075
/content/journal/jgv/10.1099/jgv.0.001075
/content/journal/jgv/10.1099/jgv.0.001075
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