The role of constitutive interferon-kappa production in antiviral defense in human skin
Active Project Grant Awarded Last action
- Award ID
- F31AI189083
- Recipient
-
University Of Massachusetts Medical School UEI MQE2JHHJW9Q8
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $70,892
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 0% complete
- Originally
- Place of performance
- Worcester, MA 01655, USA
Award details come from USAspending.gov.
Description
- Abstract
- The skin serves as an immunological barrier that protects the host from virus infection. However, little is known about the contributions of skin barrier cells, including epithelial keratinocytes and dermal fibroblasts, to antiviral defense in the skin. One way that cells protect against virus infection is through the virus-inducible expression of a class of antiviral signaling molecules known as interferons. Intriguingly, epithelial keratinocytes constitutively express a type-I interferon family member known as interferon-kappa (IFN-K) in the absence of infection, but its role in skin antiviral defense is poorly understood. Therefore, the overall objective of this proposal is to investigate the role of constitutive IFN-K production in protecting keratinocytes and fibroblasts from virus infection. In preliminary studies, we found that the herpes simplex 1 virus (HSV-1) has enhanced replication in IFN-K deficient keratinocytes at early time points during infection. We also found that keratinocyte-derived IFN-K protected dermal fibroblasts from HSV-1 infection in a human skin organoid model that recapitulates the architecture of human skin. IFN-K induced expression of the interferon-stimulated gene (ISG) IFI16, a nuclear DNA sensor that restricts HSV-1 replication, in keratinocytes but not in dermal fibroblasts. The ability of IFN-K to induce differential ISG expression in different cell types suggests distinct mechanisms by which this antiviral factor acts to protect against virus infection. Therefore, the central hypothesis of this proposal is that continuous IFN-K production by keratinocytes establishes an antiviral state in the skin by engaging cell-type specific signaling pathways in the absence of infection. This basal antiviral state serves to protect the host against future viral encounters. Here, we propose to further investigate the role of IFN-K in cutaneous antiviral defense following HSV-1 infection. In aim 1, we will determine how constitutive IFN-K production confers protection from HSV-1 infection in keratinocytes. In aim 2, we will define the contributions of IFN-K-mediated signaling pathways in protecting dermal fibroblasts from HSV-1 infection in skin organoid cultures. Collectively, the completion of these aims will reveal fundamental insight into the mechanisms by which constitutive IFN-K production and cellular communication contribute to skin antiviral defense.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $35,446 | |
| Amendment | $35,446 | |
| Original award | $0 |
Quick answers
Who received award F31AI189083?
F31AI189083 was awarded to University Of Massachusetts Medical School by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on December 4, 2026.
How much is award F31AI189083 worth?
$70,892 has been obligated on F31AI189083.
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