cGAS-STING responses are dampened in high-risk HPV type 16 positive head and neck squamous cell carcinoma cells

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Shaikh, Mushfiq H
Bortnik, Vuk
McMillan, Nigel AJ
Idris, Adi
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2019
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http://creativecommons.org/licenses/by-nc-nd/4.0/
Abstract

Head and neck cancers (HNCs) are a major health problem and a leading cause of morbidity and mortality worldwide. More than 90% of these tumours are head and neck squamous cell carcinomas (HNSCCs). Amongst the common risk factors for HNCs (tobacco and alcohol use), there is a strong association of human papillomavirus (HPV) with HNSCCs. HPV type 16 (HPV 16), the major high-risk HPV type, is most commonly associated with HPV-driven HNSCCs. The promiscuous nature of the major HPV oncogene, E7, allows its interaction with a myriad of host proteins including STING, a component of the viral DNA-sensing cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) machinery. Sensing of viral DNA by the cGAS-STING machinery results in a type I interferon (IFN)-mediated anti-viral response. Amelioration of IFN responses resulting from the direct blockade of STING by E7 was first demonstrated in high-risk HPV type 18 (HPV 18) positive (+) cervical squamous cell carcinoma (CESC) cells. However, the role of E7 from HPV 16 (HPV 16E7) in antagonising cGAS-STING responses have not been investigated, let alone in the context of HNSCCs. Here, we show that HPV 16E7+, but not HPV 16E7 negative (−), HNSCC cells respond poorly to cGAS-STING activation stimulus. We further confirm that this inhibition occurred via the highly conserved LXCXE motif in 16E7. This finding contributes to the better understanding of role of high-risk HPV E7 in blocking cGAS-STING pathway, especially in the context of HNSCCs.

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Microbial Pathogenesis
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© 2019 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
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Microbiology
Immunology
Medical microbiology
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