Snapin promotes
            <scp>HIV</scp>
            ‐1 transmission from dendritic cells by dampening
            <scp>TLR</scp>
            8 signaling

Khatamzas, Elham; Hipp, M.; Gaughan, Daniel; Pichulik, Tica; Leslie, Alasdair; Fernandes, Ricardo A.; Muraro, Daniele; Booth, Sarah; Zausmer, Kieran; Sun, Meiyi; Kessler, Benedikt M.; Rowland‐Jones, Sarah; Cerundolo, Vincenzo; Simmons, Alison

doi:10.15252/embj.201695364

Cited by 15 publications

(19 citation statements)

References 52 publications

(69 reference statements)

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“…In DCs, HIV-1 evades the detection of TLR8 by using the motilin protein Snapin. Inhibiting Snapin enhances the localization of early endosomes of HIV-1 and TLR8, triggers the proinflammatory response, and inhibits the infection of CD4 T cells [145]. These results show that TLR8 plays a critical role in innate immune sensing of HIV in DCs.…”

Section: Human Immunodeficiency Virusmentioning

confidence: 64%

Infection and atherosclerosis: TLR-dependent pathways

Xia

2020

Cell. Mol. Life Sci.

102

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Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.

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Section: Human Immunodeficiency Virusmentioning

confidence: 64%

Infection and atherosclerosis: TLR-dependent pathways

Xia

2020

Cell. Mol. Life Sci.

102

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“…Acidic environment is not a requirement for TLR8 activation. Endosomal TLR8 dimers are cleaved by neutral proteases, and studies in myeloid DCs have shown that retaining HIV or TLR8 ligands in early endosomes by preventing maturation, increases activation 34 . HIV endocytosis was not completely inhibited in our experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas plasmacytoid DCs sense endosomal HIV-1 ssRNA by TLR7 and induce protective type I interferon responses 31,72 , myeloid DCs, and macrophages sense endosomal HIV-1 ssRNA by TLR8 but fail to induce a protective immune response (e.g. type I IFNs) [33][34][35] . In the T cell zone of the lymph node, the contribution of TLR8-mediated cytokine from a large number of T cells could play a role in HIV pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

“…HIV endocytosis by plasmacytoid DCs induces TLR7 activation and type I IFN production 30 . In monocytes and myeloid DCs, TLR8 has been shown to recognize HIV ssRNA resulting in MyD88-dependent activation and subsequent interleukin (IL)-1β production [31][32][33][34][35] . Several studies show expression of TLR7 and TLR9 in CD4+ T cells [36][37][38][39] whereas inconsistent results are reported for TLR8: some studies claim that TLR8 is present in T cells 38,40 , while others show the absence of the receptor 39,41 .…”

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confidence: 99%

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Sensing of HIV-1 by TLR8 activates human T cells and reverses latency

et al. 2020

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During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.

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“…Attachment to DC‐SIGN allows virus to remain infectious for prolonged periods of time in DC (Geijtenbeek et al, ) despite the fact that DCs have a highly developed endolysosomal pathway (Blauvelt et al, ; Turville et al, ). This may at least in part be attributed to the SNARE‐associated protein Snapin downregulating toll‐like receptor 8 signalling in infected DC endosomes (Khatamzas et al, ). Instead, virus is sequestered in endosomal‐derived compartments upon maturation (Garcia et al, ; Wang et al, ).…”

Section: Virological Synapsementioning

confidence: 99%

Masters of manipulation: Viral modulation of the immunological synapse

Bayliss

Piguet

2018

Cellular Microbiology

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In order to thrive, viruses have evolved to manipulate host cell machinery for their own benefit. One major obstacle faced by pathogens is the immunological synapse. To enable efficient replication and latency in immune cells, viruses have developed a range of strategies to manipulate cellular processes involved in immunological synapse formation to evade immune detection and control T-cell activation. In vitro, viruses such as human immunodeficiency virus 1 and human T-lymphotropic virus type 1 utilise structures known as virological synapses to aid transmission of viral particles from cell to cell in a process termed trans-infection. The formation of the virological synapse provides a gateway for virus to be transferred between cells avoiding the extracellular space, preventing antibody neutralisation or recognition by complement. This review looks at how viruses are able to subvert intracellular signalling to modulate immune function to their advantage and explores the role synapse formation has in viral persistence and cell-to-cell transmission.

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Snapin promotes HIV ‐1 transmission from dendritic cells by dampening TLR 8 signaling

Cited by 15 publications

References 52 publications

Infection and atherosclerosis: TLR-dependent pathways

Infection and atherosclerosis: TLR-dependent pathways

Sensing of HIV-1 by TLR8 activates human T cells and reverses latency

Masters of manipulation: Viral modulation of the immunological synapse

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