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Activating the DNA Damage Response and Suppressing Innate Immunity: Human Papillomaviruses Walk the Line

1
Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA 23298, USA
2
VCU Massey Cancer Center, Richmond, VA 23298, USA
*
Author to whom correspondence should be addressed.
Pathogens 2020, 9(6), 467; https://doi.org/10.3390/pathogens9060467
Received: 30 April 2020 / Revised: 8 June 2020 / Accepted: 10 June 2020 / Published: 13 June 2020
Activation of the DNA damage response (DDR) by external agents can result in DNA fragments entering the cytoplasm and activating innate immune signaling pathways, including the stimulator of interferon genes (STING) pathway. The consequences of this activation can result in alterations in the cell cycle including the induction of cellular senescence, as well as boost the adaptive immune response following interferon production. Human papillomaviruses (HPV) are the causative agents in a host of human cancers including cervical and oropharyngeal; HPV are responsible for around 5% of all cancers. During infection, HPV replication activates the DDR in order to promote the viral life cycle. A striking feature of HPV-infected cells is their ability to continue to proliferate in the presence of an active DDR. Simultaneously, HPV suppress the innate immune response using a number of different mechanisms. The activation of the DDR and suppression of the innate immune response are essential for the progression of the viral life cycle. Here, we describe the mechanisms HPV use to turn on the DDR, while simultaneously suppressing the innate immune response. Pushing HPV from this fine line and tipping the balance towards activation of the innate immune response would be therapeutically beneficial. View Full-Text
Keywords: human papillomavirus; cervical cancer; head and neck cancer; DNA damage response; innate immune response; interaction human papillomavirus; cervical cancer; head and neck cancer; DNA damage response; innate immune response; interaction
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James, C.D.; Das, D.; Bristol, M.L.; Morgan, I.M. Activating the DNA Damage Response and Suppressing Innate Immunity: Human Papillomaviruses Walk the Line. Pathogens 2020, 9, 467.

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