BioinformaticsCosmosID-HUBScientificViromeDetection of Virome Variation in Skin Injury Response Using the CosmosID-HUB

8 September 2022by Barış Özdinç0

The skin is the body’s first line of defense, protecting the host against environmental or microbial insults by the imposition of a physical barrier. Upon microbial entry into wounds, innate immune cells generate antimicrobial proteins to prevent bacterial infections. A well-studied example is the innate immune circuits of IL-17 and IL-22, which are activated by wounds to produce peptides with antibacterial properties. Yet, how antiviral proteins (AVP) are regulated is understudied. Nonetheless, recent findings highlight a role of IL-27 that may induce keratinocytes in the context of cutaneous Zika virus transmission. The potential role of keratinocytes in viral transmission immunity pathways and their ability to induce antibacterial responses upon skin wound injury, led Lei et al. to investigate antiviral gene expression profiles of the keratinocytes upon acute skin injury. To do that, they compared the transcriptional profiles of wounded and non-wounded tissue samples. Using microarrays on skin samples collected at different time points, they identified an increased expression of AVPs 24 hours after the wounding. OAS2 and OASL were identified to be significantly transcriptionally active AVPs after wounding, but OAS1 and MX1 AVPs were also activated to a lesser extent, and exclusively in the epidermis, but not in the dermis. It is known that skin injury induces pain as cutaneous skin nociceptive fibers are activated. An essential nociceptor protein is TRPV1 and is known to connect the skin to the immune system. To elucidate if the TRPV1 pain receptor and antiviral responses were linked, the research group ablated TRPV1-bearing nerve fibers of mouse skin tissue using an ultra-potent capsaicin analog. The ablation of nerve fibers led to a decrease of multiple AVPs’ transcription. The findings from the ablation experiment were expanded in transgenic mice experiments. Trpv1‒/‒ transgenic mice showed decreased transcription of Oas2 and Oasl2 when compared to WT mice. Administration of capsaicin, a TRPV1 agonist, to mouse skin without injury induced Oas2 and Oasl2 transcription, proving that TRPV1 activation alone may lead to AVP production. To investigate the link between TRPV1 signaling and viral infectivity, the research group inoculated Trpv1‒/‒ and WT skin explants with HSV. Here, the loss of TRPV1 receptors sensitized skin cells to HSV infection. Analysis of the skin virome with and without wounds using the CosmosID-HUB Microbiome bioinformatics platform illustrated clear changes in the wound viral community between non-wounded skin, and wounded skin on day 0, day 14 and day 56.  In summary, the findings of the study illustrated the clear importance of the TRPV1 pain receptor on inducing the skin’s antiviral response. AVPs induced by TRPV1 activation at different skin locations resulted in dynamic variation of viral communities over the skin virome.

Lei et al. 2022. Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response.

 

Barış Özdinç

Barış Özdinç analyzes microbiome research with his educational background in genetics and evolution. As a research analyst for CosmosID, he combines metagenomics and data analyses to identify microbial biomarkers in disease cohorts and evaluate microbiome research tools. His work involves curating microbiome data and creating interesting microbiome content for newsletters and blog posts. Barış Özdinç received his bachelor’s degree in genetics and master’s degree in biodiversity, evolution, and conservation from University College London (UCL). Currently, he lives in Istanbul, Turkey, where he lives with his cat, Delight, and mentors female students in their STEM career pursuits.

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