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Lower temperatures reduce type I interferon activity and promote alphaviral arthritis.

ABSTRACT: Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, with peripheral and limb joints most commonly affected. Using a mouse model of CHIKV infection and arthritic disease, we show that CHIKV replication and the ensuing foot arthropathy were dramatically reduced when mice were housed at 30°C, rather than the conventional 22°C. The effect was not associated with a detectable fever, but was dependent on type I interferon responses. Bioinformatics analyses of RNA-Seq data after injection of poly(I:C)/jetPEI suggested the unfolded protein response and certain type I interferon responses are promoted when feet are slightly warmer. The ambient temperature thus appears able profoundly to effect anti-viral activity in the periphery, with clear consequences for alphaviral replication and the ensuing arthropathy. These observations may provide an explanation for why alphaviral arthropathies are largely restricted to joints of the limbs and the extremities.

SUBMITTER: Prow NA

PROVIDER: S-EPMC5770078 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Lower temperatures reduce type I interferon activity and promote alphaviral arthritis.

Prow Natalie A NA Tang Bing B Gardner Joy J Le Thuy T TT Taylor Adam A Poo Yee S YS Nakayama Eri E Hirata Thiago D C TDC Nakaya Helder I HI Slonchak Andrii A Mukhopadhyay Pamela P Mahalingam Suresh S Schroder Wayne A WA Klimstra William W Suhrbier Andreas A

PLoS pathogens 20171227 12

Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, with peripheral and limb joints most commonly affected. Using a mouse model of CHIKV infection and arthritic disease, we show that CHIKV replication and the ensuing foot arthropathy were dramatically reduced when mice were housed at 30°C, rather than the conventional 22°C. The effect was not associated with a detectable fever, but was dependent on type I interferon responses ...[more]

PMID: 29281739

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Project description:OBJECTIVE:Despite huge global, national, and local preventive measures including travel restriction, social distancing, and quarantines, the outbreak of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develops the coronavirus disease 2019 (COVID-19) worldwide pandemic. SARS-CoV-2 emerging from Wuhan, China, took only three months to cover >200 countries worldwide by infecting more than 2.4 million people and killing more than 150,000 people. Although this infection at the early stage creates seasonal flu-like symptoms with a higher illness, it eventually causes a higher mortality. Epidemiological studies not only find the causes of many health issues but also suggest preventive measures. This study aimed to see the link between environment temperature and COVID-19 cases. STUDY DESIGN:The monthly average environment temperature (MAET) and various COVID-19 cases of a country were collected and analyzed to see the relationship between these parameters. METHODS:Univariate analysis and statistical modeling were used to determine the relationship between environment temperature and different COVID-19 cases. RESULTS:This study found that the majorities of the countries having higher COVID-19 cases are located in the higher latitude (colder region) in the globe. As of 20th April data available, statistical analyses by various methods have found that strong negative correlations with statistical significance exist between MAET and several COVID-19 cases including total cases, active cases, and cases per million of a country (Spearman correlation coefficients were -0.45, -0.42, and -0.50 for total cases, active cases, and cases/per million, respectively). Analysis by the statistical log-linear regression model further supports that the chance of patients to contract COVID-19 is less in warmer countries than in colder countries. CONCLUSION:This pilot study proposes that cold environment may be an additional risk factor for COVID-19 cases.

Project description:Objective: The type I interferon (IFN) response in rheumatoid arthritis (RA) has been extensively studied in relation to therapy with biological DMARDs (bDMARDs). However, the effect of conventional synthetic (cs)DMARDs and glucocorticoids (GCs) on IFN response gene (IRG) expression remains largely unknown, even though csDMARDS are used throughout all disease phases, including simultaneously with biologic therapy. This study was aimed to determine the dynamics of IFN response upon immunosuppressive treatment. Methods: Whole blood was collected in PAXgene tubes from 35 RA patients who received either COBRA therapy (combination of prednisone, initially 60 mg, methotrexate and sulfasalazine) (n = 14) or COBRA-light therapy (prednisone, initially 30 mg, and methotrexate) (n = 21). Expression of 10 IRGs was determined by real-time PCR at baseline (T0), after 4 weeks (T4), and 13 weeks (T13) of treatment. IRG selection was based on the differential presence of transcription factor binding sites (TFBS), in order to study the therapy effect on different pathway components involved in IFN signaling. Results: Seven of the 10 IRGs displayed significant changes during treatment (p ≤ 0.016). These 7 IRGs all displayed a particularly pronounced decrease between T0 and T4 (≥1.6-fold, p ≤ 0.0059). The differences between IRG sensitivity to the treatment appeared related to the presence of TFBS for STAT1 and IRF proteins within the genes. The extent of the decreases between T0 and T4 was similar for the COBRA- and COBRA-light-treated group, despite the differences in drug combination and doses in those groups. Between T4 and T13, however, IRG expression in the COBRA-light-treated group displayed a significant increase, whereas it remained stable or decreased even further in most COBRA-treated patients (comparison of mean fold changes, p = 0.011). A significant association between IRG dynamics and clinical response to therapy was not detected. Conclusions: Immunosuppressive treatment with csDMARDs, in this case a combination of prednisolone, methotrexate and sulfasalazine, substantially downregulates the IFN response in RA patients. The dynamics of this downregulation were partly dependent on the presence of TFBS within the IRGs and the combination and dosages of agents, but they were irrespective of the clinical response to therapy.

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Lower temperatures reduce type I interferon activity and promote alphaviral arthritis.

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Lower temperatures reduce type I interferon activity and promote alphaviral arthritis.

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