Hantaan virus can infect human keratinocytes and activate an interferon response through the nuclear translocation of IRF-3

- Hantaan virus replicates in HaCaT cells.
- Hantaan virus induce antiviral IFNβ is IRF3 dependent.
- Hantaan virus induce CXCL10 independent of IFN activation in HaCaT cells.

Hantaan virus (HTNV) is a rodent-borne virus that causes hemorrhagic fever with renal syndrome (HFRS) in Asia and can be transmitted to humans through bites or the inhalation of aerosolized urine, droppings, or saliva of infected rodents. Keratinocytes predominate in the epidermis and reportedly serve as a replication site for multiple vector-borne viruses, little is known about the susceptibility of human skin cells to HTNV infection. Therefore, we aimed to evaluate whether human keratinocytes support HTNV replication and elicit an immune response against HTNV infection. We found that a human keratinocyte cell line, HaCaT, supports HTNV replication. In addition, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (MDA5) play key roles in the detection of HTNV infection in HaCaT cells and in the up-regulation of interferon (IFN)-β expression, which subsequently leads to the production of a large amount of antiviral interferon-stimulated genes (ISGs) and other chemokines used for immune cell recruitment. Furthermore, we suggest that interferon regulatory factor (IRF)-3, as opposed to NF-κB/p65 or IRF-7, is translocated to the nucleus to induce IFN-β. However, the early induction of chemokine CXCL10 was a direct result of HaCaT cells counteracting HTNV infection and was not due to the induction of IFN. Overall, our data demonstrate, for the first time, the permissiveness of human keratinocytes to HTNV infection.