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Viruses 2019, 11(4), 330; https://doi.org/10.3390/v11040330

Critical Role of an MHC Class I-Like/Innate-Like T Cell Immune Surveillance System in Host Defense against Ranavirus (Frog Virus 3) Infection

1
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
2
The Norwegian College of Fishery Science, University of Tromsø, the Arctic university of Norway, 9037, Tromsø, Norway
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 18 March 2019 / Revised: 31 March 2019 / Accepted: 3 April 2019 / Published: 6 April 2019
PDF [1508 KB, uploaded 6 April 2019]

Abstract

Besides the central role of classical Major Histocompatibility Complex (MHC) class Ia-restricted conventional Cluster of Differentiation 8 (CD8) T cells in antiviral host immune response, the amphibian Xenopus laevis critically rely on MHC class I-like (mhc1b10.1.L or XNC10)-restricted innate-like (i)T cells (iVα6 T cells) to control infection by the ranavirus Frog virus 3 (FV3). To complement and extend our previous reverse genetic studies showing that iVα6 T cells are required for tadpole survival, as well as for timely and effective adult viral clearance, we examined the conditions and kinetics of iVα6 T cell response against FV3. Using a FV3 knock-out (KO) growth-defective mutant, we found that upregulation of the XNC10 restricting class I-like gene and the rapid recruitment of iVα6 T cells depend on detectable viral replication and productive FV3 infection. In addition, by in vivo depletion with XNC10 tetramers, we demonstrated the direct antiviral effector function of iVα6 T cells. Notably, the transitory iV6 T cell defect delayed innate interferon and cytokine gene response, resulting in long-lasting negative inability to control FV3 infection. These findings suggest that in Xenopus and likely other amphibians, an immune surveillance system based on the early activation of iT cells by non-polymorphic MHC class-I like molecules is important for efficient antiviral immune response.
Keywords: Unconventional T cell; nonclassical MHC; antiviral immunity; interferon Unconventional T cell; nonclassical MHC; antiviral immunity; interferon
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Edholm, E.-S.; De Jesús Andino, F.; Yim, J.; Woo, K.; Robert, J. Critical Role of an MHC Class I-Like/Innate-Like T Cell Immune Surveillance System in Host Defense against Ranavirus (Frog Virus 3) Infection. Viruses 2019, 11, 330.

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