Lymphotoxins and cytomegalovirus cooperatively induce interferon-β, establishing host-virus détente

Benedict, Chris A, Banks, Theresa A, Senderowicz, Lionel, Ko, Mira, Britt, William J, Angulo, Ana, Ghazal, Peter ORCID: https://orcid.org/0000-0003-0035-2228 and Ware, Carl F 2001. Lymphotoxins and cytomegalovirus cooperatively induce interferon-β, establishing host-virus détente. Immunity 15 (4) , pp. 617-626. 10.1016/S1074-7613(01)00222-9

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Abstract

Tumor necrosis factor (TNF)-related cytokines regulate cell death and survival and provide strong selective pressures for viruses, such as cytomegalovirus (CMV), to evolve counterstrategies in order to persist in immune-competent hosts. Signaling by the lymphotoxin (LT)-β receptor or TNF receptor-1, but not Fas or TRAIL receptors, inhibits the cytopathicity and replication of human CMV by a nonapoptotic, reversible process that requires nuclear factor κB (NF-κB)-dependent induction of interferon-β (IFN-β). Efficient induction of IFN-β requires virus infection and LT signaling, demonstrating the need for both host and viral factors in the curtailment of viral replication without cellular elimination. LTα-deficient mice and LTβR-Fc transgenic mice were profoundly susceptible to murine CMV infection. Together, these results reveal an essential and conserved role for LTs in establishing host defense to CMV.

Item Type:	Article
Date Type:	Publication
Status:	Published
Publisher:	Elsevier (Cell Press)
ISSN:	1074-7613
Last Modified:	23 Oct 2022 14:27
URI:	https://orca.cardiff.ac.uk/id/eprint/113724

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