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La Crosse Virus Infection of Human Keratinocytes Leads to Interferon-Dependent Apoptosis of Bystander Non-Infected Cells In Vitro

Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA
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Author to whom correspondence should be addressed.
Viruses 2020, 12(3), 253; https://doi.org/10.3390/v12030253
Received: 5 February 2020 / Revised: 20 February 2020 / Accepted: 21 February 2020 / Published: 25 February 2020
Resident cells in the skin serve as the first innate line of defense against insect-borne pathogens, but the role of these cell types in promoting or limiting arbovirus replication is not completely understood. Here, we have examined the outcome of infection of cultured human keratinocyte cells with La Crosse virus (LACV), using a spontaneously transformed cell line, HaCaT. In single cycle infections, keratinocyte HaCaT cells supported rapid and high level LACV replication, resulting in high virus yields and extensive caspase-dependent cell death. By contrast, multi-cycle LACV replication in HaCaT cells was restricted by an antiviral response elicited by the production of both IFN-β and IFN-λ. During low multiplicity LACV infections, HaCaT cell death was seen in non-infected bystander cells. Media from LACV-infected cells induced caspase-dependent killing of naïve non-infected HaCaT cells, and this bystander cell death was relieved by IFN-β neutralizing antibodies or by an inhibitor of JAK-STAT signaling. Naïve HaCaT cells showed dose-dependent killing by treatment with exogenous IFN-β but not IFN-λ. Our data suggest a model whereby keratinocytes produce IFNs which limit virus spread through both antiviral signaling and by induction of bystander cell death of potential new target cells for infection. View Full-Text
Keywords: La Crosse virus; keratinocytes; interferon; bystander cell death La Crosse virus; keratinocytes; interferon; bystander cell death
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MDPI and ACS Style

Cruz, M.A.; Parks, G.D. La Crosse Virus Infection of Human Keratinocytes Leads to Interferon-Dependent Apoptosis of Bystander Non-Infected Cells In Vitro. Viruses 2020, 12, 253. https://doi.org/10.3390/v12030253

AMA Style

Cruz MA, Parks GD. La Crosse Virus Infection of Human Keratinocytes Leads to Interferon-Dependent Apoptosis of Bystander Non-Infected Cells In Vitro. Viruses. 2020; 12(3):253. https://doi.org/10.3390/v12030253

Chicago/Turabian Style

Cruz, Maria A., and Griffith D. Parks 2020. "La Crosse Virus Infection of Human Keratinocytes Leads to Interferon-Dependent Apoptosis of Bystander Non-Infected Cells In Vitro" Viruses 12, no. 3: 253. https://doi.org/10.3390/v12030253

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