RNase 7 combined with human self-DNA uniquely induced IP-10 through IFN-β/STING signaling in keratinocytes, providing antiviral protection against herpes simplex virus.
Unique antiviral functionRNase 7 activates STING-mediated antiviral defense when combined with self-DNA — a capability not shared by other skin antimicrobial peptides
What the researchers found
RNase 7 combined with human self-DNA strongly induced IP-10 production in keratinocytes. Notably, two other antimicrobial peptides (human beta-defensin 2 and LL-37) combined with DNA did not produce this effect, showing RNase 7 has a unique ability.
The IP-10 production was mediated through type I interferon (IFN-beta) induction and the STING pathway (stimulator of interferon genes). Blocking the interferon receptor or STING significantly reduced the response.
Pretreating keratinocytes with RNase 7 and DNA significantly reduced herpes simplex virus-1 infection, demonstrating a direct antiviral protective function. RNase 7 functions as an alarmin that converts self-DNA into a danger signal activating innate antiviral immunity directly in skin cells.
Why it matters
This reveals a new immune function for RNase 7 beyond its known ability to kill bacteria. By helping skin cells recognize their own DNA as a danger signal, RNase 7 activates a built-in antiviral defense system. This could be important for understanding how skin resists viral infections like herpes.
The STING pathway activation is particularly interesting because it connects an antimicrobial peptide to one of the body's most important antiviral sensing mechanisms.
The numbers in context
RNase 7 + DNA induced IP-10 via IFN-beta/STING; hBD2 and LL-37 did not; significantly reduced HSV-1 infection
How the study worked
This was a cell biology study using human keratinocyte cultures. Researchers stimulated keratinocytes with RNase 7 and human DNA, measuring IP-10 and IFN-beta production. They used blocking antibodies against the interferon receptor and STING pathway inhibitors. Antiviral activity was tested using herpes simplex virus-1 infection of keratinocytes.
Who was studied
Human keratinocyte cultures
What this study cannot tell us
This was a cell culture study. Whether RNase 7 activates the same antiviral pathway in intact human skin is unknown. The herpes virus protection was shown in pretreated cells, which may not reflect natural infection dynamics.
The study did not test whether RNase 7 protects against other viruses beyond HSV-1.
How to read the evidence
Moderate evidence from well-designed cell biology experiments with functional viral protection demonstrated.
When this study was published
Published in 2020. RNase 7 antiviral functions are being further characterized.
The bigger picture
RNase 7 is one of the most abundant antimicrobial peptides in human skin. Discovering it has a unique antiviral function — distinct from other skin AMPs — reveals a previously unknown layer of skin immune defense and could inform treatments for herpes and other skin viral infections.
Questions still open
- Does RNase 7 deficiency predispose to herpes skin infections?
- Could RNase 7 supplementation protect immunocompromised patients from skin viruses?
- Is this mechanism active against other skin-tropic viruses beyond HSV-1?
Common questions
How does skin fight viruses?
Could this help treat cold sores?
Read the original research
RNase 7 Promotes Sensing of Self-DNA by Human Keratinocytes and Activates an Antiviral Immune Response.
The Journal of investigative dermatology, 140(8), 1589-1598.e3
Citation
Kopfnagel, Verena; Dreyer, Sylvia; Baumert, Kathrin; Stark, Maximilian; Harder, Jürgen; Hofmann, Karsten; Kleine, Michael; Buch, Anna; Sodeik, Beate; Werfel, Thomas. (2020). RNase 7 Promotes Sensing of Self-DNA by Human Keratinocytes and Activates an Antiviral Immune Response.. The Journal of investigative dermatology, 140(8), 1589-1598.e3. https://doi.org/10.1016/j.jid.2019.09.029