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Lactate inhibits MAVS. 40 / 42
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"METTL3 then enhances the translation of JAK1 mRNA via m6A modification, continuously activating the JAK1/STAT3 pathway to solidify immunosuppressive functions. xref In pancreatic cancer, lactate induces ENSA‐K63la, activating the STAT3/CCL2 axis to drive TAM transcriptional reprogramming. xref Furthermore, lactate can target and inhibit MAVS proteins, blocking type I interferon production. xref Educated macrophages then turn into tumour accomplices, secreting factors like CCL2 and IL‐6. xref , xref Tumour cells maintain this environment through mechanisms such as SETDB1‐mediated stability of MCT1. xref Targeting this axis via LDHA inhibition, xref , xref blocking MCT1/4, xref or using nano‐platforms xref is a key strategy for reversing the pro‐tumour phenotype."
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"Interestingly, lactate inhibits oligomerization of MAVS, the adapter molecule for RLRs, and dampens RLR signalling [56]."
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"While lncRNAs may regulate the HK-dependent lactate production by upstream kinase stimulation, MAVS is inhibited by HK and lactate ( xref )."
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"Lactate was shown to directly bind MAVS, preventing MAVS aggregation and inhibiting type I IFN production ( Zhang et al., 2019 )."
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"On the contrary, lactate as the product of anaerobic glycolysis can directly bind to MAVS transmembrane (TM) domain and prevent MAVS aggregation."
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"Lactate negatively regulates RLR activation by targeting MAVS [28]."
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"Lactate directly inhibits MAVS resulting in reduced class I interferon production ( xref ) and in addition, exerts immunosuppressive effects (Ivashkiv,  xref )."
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"Remarkably, viral infections promote glycolysis, and excess lactate inhibits MAVS and type I IFN production by binding to the transmembrane (TM) domain of MAVS directly and preventing its aggregation."
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"Another article reported that lactate is a natural suppressor of RLR signaling targeting MAVS (Zhang et al., 2019)."
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"Excess lactate from glycolysis inhibits mitochondrial antiviral signaling (MAVS), further facilitating viral replication (331)."
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"9 Lactate, a product of glucose metabolism, inhibits the antiviral response by affecting MAVS localization through binding with its transmembrane domain (TM) and preventing the interaction of RIG‐I with MAVS."
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"Glycolysis-induced lactate production inhibits retinoic acid-inducible gene 1 (RIG-I) ( Zhang et al., 2019 ) and mitochondrial anti-viral signaling (MAVS) protein ( Yasukawa et al., 2020 ), both requi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"For instance, lactate can inhibit MAVS, and can influence a range of biological processes through its role in lactylation ."
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"In contrast, excess lactate production inhibits MAVS and the downstream antiviral immune response, facilitating viral replication (53, 54)."
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"In order to unravel the underlying mechanism by which lactate inhibits RIG-I-MAVS induced RLR activation, we explored whether lactate impacts the mitochondria localization of MAVS by binding to its TM domain, ( xref )."
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"While lncRNAs may regulate the HK-dependent lactate production by upstream kinase stimulation, MAVS is inhibited by HK and lactate (Ren et al., 2021)."
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"A recent study has shown that lactate can reduce mitochondrial antiviral signaling protein (MAVS) and downstream NF-κB activation through retinoic acid-inducible gene 1 (RIG-I) lactylation (89)."
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"Mitochondrial antiviral signaling protein (MAVS) is inhibited by the glycolytic product lactate and glycolytic enzyme HK2, thus suppressing the innate immune activation downstream of cytosolic double-stranded (ds)RNA [88,89]."
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"What is more, MAVS is inhibited by HK2 and lactate, while LncRNA may regulate HK2- or LDHA-dependent lactate production via upstream kinase stimulation."
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"A notable description of lactate as a signalling immunometabolite was the discovery that lactate suppresses mitochondrial antiviral signalling protein (MAVS) activation [36]."
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"For instance, excessive lactate production from the glycolytic pathway impairs the aggregation of MAVS."
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"In this study, we demonstrate a novel mechanism of PRRSV-mediated immune escape, which utilizes lactate produced by the glycolytic pathway to block the antiviral function of MAVS."
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"Moreover, enhanced aerobic glycolysis and lactate accumulation in this context may further inhibit MAVS activation, as described in a non-infectious context (47), thereby restraining the activation of the anti-viral RIG-I/MAVS pathway."
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"Collectively, we conclude that lactate serves as a key metabolite to mediate the promotion effect of glycolysis on PRRSV replication in Marc-145 cells.It was reported that lactate suppresses RLR activ[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Mechanistically, PRRSV promotes the expression of HK2 to produce lactate, which in turn inhibits MAVS activation and downstream type I IFN production."
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"213 Lactate produced by host glucose metabolism inhibits mitochondrial localization of MAVS and RLR activation, 214 suggesting that the mitochondrial antiviral response is linked to energy metabolism.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Also, lactate can directly interact with the mitochondrial antiviral-signaling (MAVS) protein, preventing MAVS aggregation and therefore reducing type I interferon production during RIG-I-like receptor (RLR) signaling (Zhang et al., 2019b)."
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"Excess lactate blocks the antiviral MAVS entry into the mitochondrion through the TOM70 pore."
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"Mechanistically, PRRSV promotes the expression of HK2 to produce lactate, which in turn inhibits MAVS activation and downstream type I IFN production.Viral infection as a cellular stress can induce ch[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This lactate reduces MAVS and downstream NF-κB activation through RIG-I lactylation, which in turn reduces Nlrp3 activation, induces M2 polarization in macrophages, and promotes Treg differentiation."
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"A previous study reported that lactate inhibits RLR signal activation by directly targeting the TM domain of the MAVS ( Zhang et al., 2019b )."
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"Moreover, lactate inhibits RLR signaling by binding the mitochondrial antiviral-signaling protein (MAVS) transmembrane domain and preventing MAVS aggregation, thereby promoting homeostatic macrophage polarization by indirectly suppressing type I IFN production [54, 63]."
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"Inhibition of lactate generation by oxamate potentiated MAVS mitochondria localization, but lactate add-back compromised this effect (XREF_FIG and XREF_FIG)."
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"The virus infection promotes the glycolytic pathway to produce lactate, which further suppresses the innate immune response by blocking the function of MAVS."
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"What is more, MAVS is inhibited by HK2 and lactate, while LncRNA may regulate HK2- or LDHA-dependent lactate production via upstream kinase stimulation."
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"Lactate negatively regulates RLR-mitochondrial antiviral signaling protein (MAVS) signaling and following reactions.Figure 4: Interaction of lncRNA with RIG-I-MAVS pathway."
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"In addition to its link with cancer [ 16 ], lactate can inhibit CD8+ T-cell migration through an immunosuppressive mechanism [ 17 ] and suppress innate immunity by targeting MAVS in the RLR pathway [ [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Under physiological conditions, the interaction between hexokinase II (HK2), a key rate-limiting enzyme for glycolysis and located on the mitochondrial outer membrane, and MAVS maintains HK2 activity in its basal state, which ensures the operation of glycolysis metabolism and the suppression of MAVS mediated by lactate."
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"In addition, MAVS aggregation can be suppressed by lactate [78] and TRIM31 is known to bind with phosphotidyethanolamine [79]."
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"As a second example, lactate, which is produced during aerobic glycolysis and has virus restricting activity XREF_BIBR, XREF_BIBR, also directly inhibits MAVS activity; thus lactate both reduces levels of viral PAMPs and has a negative regulatory function to inhibit PAMP driven signalling and interferon expression 128."
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