To survive, viruses have evolved the capacity to utilize various strategies that inhibit NF-B activity, including targeting receptors, adaptor proteins, IKKs, IB, and p50/p65. mechanism of immune evasion that involves the suppression of NF-B activation to provide new insights into and references for the control and prevention of viral diseases. strong class=”kwd-title” Keywords: NF-B, viruses, NF-B inhibitors, HIV-1, immune evasion 1. Introduction The nuclear factor-B (NF-B) family is composed of five related transcription factors: p50, p52, p65, c-Rel, and RelB. The activation of classical NF-B signaling involves the NF-B dimer p50/p65, but nonclassical NF-B signaling involves p52/RelB. In the classical NF-B signaling pathway, signaling molecules include NF-B (IB) kinases (IKKs), IB, p50/p65, and IKK upstream receptors and adaptor proteins. The major receptors are toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I), tumor necrosis factor (TNF) receptor (TNFR), and interleukin 1 receptor type 1 (IL-1R1), and the major adaptor proteins are myeloid differentiation primary response gene 88 (MyD88), Toll/IL-1 receptor (TIR)-containing adaptor-inducing IFN (TRIF), and mitochondrial antiviral signaling Escitalopram oxalate protein (MAVS). The innate immune system is the first line of defense against foreign pathogens. NF-B plays a major role in innate immune responses by inducing antiviral genes, such as interferon (IFN) and IFN-stimulated genes (ISG). Additionally, NF-B also promotes viral gene transcription that is harmful to some viruses latency. Therefore, over the long course of evolution, viruses have developed multiple methods that interfere with NF-B activity to promote viral survival. In this review, we focus on a viral immune evasion mechanism that functions by suppressing NF-B activation, including targeting receptors, adaptor proteins, IKKs, IB, and p50/p65. Additionally, we describe several specific NF-B inhibitors, including NS3/4, 3C and 3C-like proteases, viral deubiquitinating enzymes (DUBs), phosphodegron-like (PDL) motifs, viral protein phosphatase (PPase)-binding proteins, and small hydrophobic (SH) proteins. To better understand the role of NF-B in viral immune escape, we use human immunodeficiency virus 1 (HIV-1) as an example, and describe how inhibiting NF-B activity promotes HIV-1 immune escape in different viral life cycles: productive infection and latent infection. We hope that this review can provide a reference for the prevention and control of viral diseases. 2. The Activation of the NF-B Classical activation of NF-B needs the activation of receptors, adaptor proteins, IKKs, IB, and p50/p65 (Figure 1). When cellular receptors sense external stimuli, they transmit Escitalopram oxalate signals to the IKKs via adaptor proteins, resulting in the phosphorylation of IKKs, degradation of IB, nuclear transfer of p50/p65, and activation of NF-B. Open in a separate window Figure 1 The activation of the NF-B. The major upstream receptors of NF-BTLRs, RIG-I, TNFR, and IL-1R1sense external stimuli and transmit signals to their adaptor proteins. Rabbit Polyclonal to CNTD2 TLRs transmit signals to MyD88 or TRIF, RIG-I to MAVS, TNFR1 to receptor interacting protein 1 (RIP1), and IL-1R to MyD88. Then, MyD88 activates interleukin-1 receptor-associated kinases (IRAKs) and TNFR-associated factor 6 (TRAF6), MAVS interacts with TRAF6, and TRIF interacts with RIP1. TRAF6 and RIP1 both activate the transforming growth factor (TGF)–activated kinase 1 (TAK1) complex. The activated TAK1 complex then activates IKKs, resulting in the phosphorylation and degradation of IB and the release of p50/p65. The released p50/p65 enters the nucleus, binds specific DNA sequences, and activates NF-B transcriptional activity. 2.1. Receptors The activation of NF-B is initiated by Escitalopram oxalate receptors, such as TLRs, RIG-I, TNFR, and IL-1R1. All TLRs are type I transmembrane proteins containing three regions: the Escitalopram oxalate extracellular, intracytoplasmic, and transmembrane regions. The extracellular region recognizes the external stimulus, and the intracytoplasmic region then transmits signals to downstream adaptor molecules via the TIR domain [1]. TLR3 recruits TRIF, and TLR5, TLR7, and TLR9 recruit MyD88. TLR2 recruits MyD88 and TIR-containing adaptor protein (TIRAP, also known as MAL), and TLR4 recruits MyD88, TIRAP, TRIF, and TRIF-related adaptor molecule (TRAM) [2]. RIG-I contains two N-terminal.