Anti-viral and pro-inflammatory functions of Toll-like receptors during gamma-herpesvirus infections

Abstract

Toll-like receptors (TLRs) control anti-viral responses both directly in infected cells and in responding cells of the immune systems. Therefore, they are crucial for responses against the oncogenic γ-herpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus and the related murine virus MHV68, which directly infect immune system cells. However, since these viruses also cause lifelong persistent infections, TLRs may also be involved in modulation of inflammation during latent infection and contribute to virus-driven tumorigenesis. This review summarizes work on both of these aspects of TLR/γ-herpesvirus interactions, as well as results showing that TLR activity can drive these viruses’ re-entry into the replicative lytic cycle.

CITE-seq reveals inhibition of NF-κB pathway in B cells from vitamin D-treated multiple sclerosis patients

“…Pathway analysis also showed distinct regulations by vitamin D of several MAPK, TLR and interleukin pathways in naive and memory B-cells. In naive B-cells, we found that vitamin D treatment down-regulates interleukin-1 signaling and TLR 1/2 and TLR9 pathways known to stimulate NF-κB signaling (32). NF-κB, MAP kinase, IRF7, and PI3 kinase pathways are known to be stimulated via latent membrane protein 1 (LMP1), a mechanism favoring B-cell immortalization during chronic EBV infection (33).…”

Epstein-Barr virus: the mastermind of immune chaos

“…In the scenario of the primary EBV infection, TLRs assume a crucial function by facilitating the initial identification of the virus within innate immune cells ( 110 ). For example, TLR9 recognizes EBV nucleic acids and activates signaling pathways that lead to the production of pro-inflammatory cytokines, such as type I interferon (IFN-I) or transforming growth factor (TGF), which triggers the antiviral immune response ( 111 ). Conversely, EBV employs cunning tactics to slip through the notice of these PRRs, masterfully reshaping the immune response to its advantage ( Figure 2 ).…”

Epstein-Barr virus infection: the micro and macro worlds

“…EBV can reduce TLR expression and/or signal transduction to escape cellular immune responses to TLR activation [ 67 ]. Fathallah et al found that the EBV oncoprotein LMP1 is a strong inhibitor of TLR9 transcription, and its overexpression regulates NF-κB pathway activation, thereby reducing TLR9 promoter activity and its mRNA and protein expression levels [ 68 ].…”