Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

Silva, Mariana Ruiz; Ende-Metselaar, Heidi van der; Mulder, Henk; Smit, Jolanda M.; Rodenhuis-Zybert, Izabela A.

doi:10.1038/srep32288

Cited by 53 publications

(40 citation statements)

References 53 publications

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“…Vero E6 cells, a kindly gift from Jolanda Smit [ 34 , 35 ], were maintained with Dulbecco’s Modified Eagle Medium (DMEM, Gibco, Waltham, MA, USA) containing 5% fetal calf serum (FCS, Gibco). The used PEDV strain was CV777, and it was grown as previously described in Vero E6 cells [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Ultrastructural Characterization of Membrane Rearrangements Induced by Porcine Epidemic Diarrhea Virus Infection

Cong

Veenendaal

Klumperman

et al. 2017

Viruses

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The porcine epidemic diarrhea virus (PEDV) is a coronavirus (CoV) belonging to the α-CoV genus and it causes high mortality in infected sucking piglets, resulting in substantial losses in the farming industry. CoV trigger a drastic reorganization of host cell membranes to promote their replication and egression, but a detailed description of the intracellular remodeling induced by PEDV is still missing. In this study, we examined qualitatively and quantitatively, using electron microscopy, the intracellular membrane reorganization induced by PEDV over the course of an infection. With our ultrastructural approach, we reveal that, as most of CoV, PEDV initially forms double-membrane vesicles (DMVs) and convoluted membranes (CMs), which probably serve as replication/transcription platforms. Interestingly, we also found that viral particles start to form almost simultaneously in both the endoplasmic reticulum and the large virion-containing vacuoles (LVCVs), which are compartments originating from the Golgi, confirming that α-CoV assemble indistinguishably in two different organelles of the secretory pathway. Moreover, PEDV virons appear to have an immature and a mature form, similar to another α-CoV the transmissible gastroenteritis coronavirus (TGEV). Altogether, our study underlies the similarities and differences between the lifecycle of α-CoV and that of viruses belonging to other CoV subfamilies.

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Section: Methodsmentioning

confidence: 99%

Ultrastructural Characterization of Membrane Rearrangements Induced by Porcine Epidemic Diarrhea Virus Infection

Cong

Veenendaal

Klumperman

et al. 2017

Viruses

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“…CHIKV infects many organs and cell types 10 , induces apoptosis and direct tissue damage 12, 13 14 . The acute phase is also associated with robust innate immune responses, leading to high levels of type I IFNs, proinflammatory cytokines/chemokines, growth factors 12, 15 16 17 18 19 , and immune cell infiltration 10 . In the chronic phase, CHIKV arthritis may progress without active viral replication and is characteristic of elevated cytokines and immune cell infiltration 10, 20 .…”

Section: Introductionmentioning

confidence: 99%

Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy

Yang

Geng

Yang

et al. 2020

Preprint

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35Macrophage scavenger receptor 1 (MSR1) mediates the endocytosis of modified low-density 36 lipoproteins and plays an important antiviral role. However, the molecular mechanism underlying 37 MSR1 antiviral actions remains elusive. Herein, we report that MSR1 activates autophagy to 38 restrict infection of Chikungunya virus (CHIKV), an arthritogenic alphavirus that causes acute and 39 chronic crippling arthralgia. Msr1 expression was rapidly upregulated after CHIKV infection in 40 mice. Msr1 knockout mice had elevated viral loads and increased susceptibility to CHIKV arthritis 41 along with a normal type I IFN response. Induction of LC3 lipidation by CHIKV, a marker of 42 autophagy, was reduced in Msr1 -/cells. Mechanistically, MSR1 interacted with ATG12 through 43 its cytoplasmic tail and this interaction was enhanced by CHIKV nsP1 protein. MSR1 repressed 44 CHIKV replication through ATG5-ATG12-ATG16L1 and this was dependent on the FIP200-and-45 WIPI2-binding domain, but not the WD40 domain of ATG16L1. Our results elucidate an antiviral 46 role for MSR1 involving the autophagic function of ATG5-ATG12-ATG16L1. 47 48 Keywords: macrophage scavenger receptor, MSR1, Chikungunya virus, autophagy, ATG 49 50 51 Macrophage scavenger receptor 1 (MSR1) is a member of the scavenger receptor family, 52 members of which are structurally heterogeneous with little or no homology. They are grouped 53 into the same family due to their shared functional properties such as the ability to bind and 54 internalize a diverse range of self-and non-self-ligands including modified low density lipoproteins 55 (LDL), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) 1 . The ligand promiscuity of these 56 scavenger receptors is probably due to their function as components of other pathogen pattern 57 recognition receptor (PRR) signaling complexes. For example, MSR1 interacts with Toll-like 58 receptor (TLR) 4 and TLR2 to promote phagocytosis of Gram-positive and negative bacteria, 59 respectively 2 , and is required for LPS-induced TLR4 signaling 3 . However, the current literature 60 about the physiological function of MSR1 in viral infections is inconsistent. MSR1 could recognize 61 extracellular viral nucleic acids, mediating their endocytosis and presenting them to TLR3/9, 62 thereby triggering a type I interferon (IFN-I) response in both infected and uninfected cells 4, 5 . 63 MSR1 limits herpes simplex virus 1 infection likely by regulating macrophage adherence in vivo 64 6 , whereas it controls adenovirus type 5-elicited hepatic inflammation and fibrosis by promoting 65 M2 macrophage polarization 7 . MSR1 could contribute to pathogenesis of murine hepatitis virus-66 induced fulminant hepatitis by activating neutrophil-mediated complement 8 . Ectopic expression 67 of MSR1 inhibited Sindbis virus A and human parainfluenza virus type 3 in STAT1 -/fibroblasts 9 , 68 suggesting an IFN-I-independent antiviral role for MSR1. These contrasting results suggest that 69 the antiviral mechanisms of MSR1 vary with viral species and disease mod...

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“…To elucidate the mechanism of monocyte shift during CHIKV infection, we first assessed the contribution of CHIKV particle sensing and/or infection to monocyte subset distribution. We studied monocytes in the context of PBMCs as other cell subsets have previously been shown to be important for the function of monocytes during CHIKV infection[4,5]. PBMCs were isolated from seven donors, as described previously[4] and infected with CHIKV strain LR2006 OPY1 (from hereon called CHIKV) at (multiplicity of infection) MOI 10.…”

Section: Resultsmentioning

confidence: 99%

“…The exact mechanism underlying CHIKV-mediated pathogenesis is not completely understood, however, clinical and in vivo studies describe local joint inflammation, infiltration of monocytes into the synovial cavity and bone resorption due to increased osteoclast activity[1–3]. Monocytes represent important cellular targets of CHIKV replication in the blood[4,5], and tissue infiltrating monocytes and tissue-resident macrophages have been postulated to act as a vehicles and a reservoir for chronic CHIKV RNA/antigens, respectively [6,7].…”

Section: Introductionmentioning

confidence: 99%

Rewiring PBMC responses to prevent CHIKV infection-specific monocyte subset redistribution and cytokine responses

Aguilar-Briseño

Silva

Moser

et al. 2020

Preprint

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19Infection with the mosquito-borne Chikungunya virus (CHIKV) causes acute or chronic 20 arthritis in humans. Inflammatory responses mediated by monocytes, the primary target 21 cells of CHIKV infection in the blood, are considered to play an important role in CHIKV 22 pathogenesis. A recent study revealed that the acute phase of CHIKV infection is 23 characterized by a monocyte-driven response, with an expansion of the intermediate 24 monocyte (IM) subset. In this study, we adopted a previously established in vitro model 25 of CHIKV infection in peripheral blood mononuclear cells, to elucidate the mechanism and 26 relevance of IM expansion in CHIKV replication and associated inflammatory responses. 27 Our data show that infectious but not replication-incompetent CHIKV increases the 28 frequency of IM and to a lesser extent, non-classical (NM) monocytes while reducing the 29 number of classical monocytes (CM). The increase of IM or NM frequency coincided with 30 the activation of inflammatory response and occurred in the absence of lymphocytes 31 implying that monocyte-derived cues are sufficient to drive this effect. Importantly, 32 priming of monocytes with LPS prevented expansion of IM and NM but had no effect on 33 viral replication. It did however alter CHIKV-induced cytokine signature. Taken together, 34 our data delineate the role of IM in CHIKV infection-specific innate immune responses 35 and provide insight for the development of therapeutic strategies that may focus on 36 rewiring monocyte immune responses to prevent CHIKV-mediated arthralgia and 37 arthritis. 38 39 Over the last decade, chikungunya virus (CHIKV) infection has affected millions of people 40 worldwide[1]. The vast majority of infected patients experience a febrile illness with 41 painful joints. A substantial number of these individuals, however, develop persistent 42 arthritis-like manifestations (12-49%)[1]. The exact mechanism underlying CHIKV-43 mediated pathogenesis is not completely understood, however, clinical and in vivo 44 studies describe local joint inflammation, infiltration of monocytes into the synovial 45 cavity and bone resorption due to increased osteoclast activity[1-3]. Monocytes 46 represent important cellular targets of CHIKV replication in the blood[4,5], and tissue 47 infiltrating monocytes and tissue-resident macrophages have been postulated to act as a 48 vehicles and a reservoir for chronic CHIKV RNA/antigens, respectively [6,7]. 49 As innate sentinels of their host, blood monocytes sense invading pathogens and 50 orchestrate innate immune responses to contain their spread as well as setting the scene 51 for the activation of adaptive immune responses[8]. Via a set of pathogen recognition 52 receptors (PRRs), monocytes are able to detect a variety of complex pathogen associated 53 molecular patterns (PAMPS). Engagement of PRRs triggers several cellular signaling 54 cascades resulting in cell differentiation, release of inflammatory mediators and/or 55 programmed cell death[8-10]. 56 Monocytes can be divi...

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Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

Cited by 53 publications

References 53 publications

Ultrastructural Characterization of Membrane Rearrangements Induced by Porcine Epidemic Diarrhea Virus Infection

Ultrastructural Characterization of Membrane Rearrangements Induced by Porcine Epidemic Diarrhea Virus Infection

Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy

Rewiring PBMC responses to prevent CHIKV infection-specific monocyte subset redistribution and cytokine responses

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