Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model.

Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model.
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DOI:
10.1038/s41467-021-22930-6
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发表时间:
2021-05-24
影响因子:
16.6
通讯作者:
Diehl SA
Diehl SA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hanley JP;Tu HA;Dragon JA;Dickson DM;Rio-Guerra RD;Tighe SW;Eckstrom KM;Selig N;Scarpino SV;Whitehead SS;Durbin AP;Pierce KK;Kirkpatrick BD;Rizzo DM;Frietze S;Diehl SA

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大约20-25%的登革病毒(DENV)感染会出现从自限性发热到休克等症状。在严重登革热进展过程中的免疫基因表达变化已在住院患者中记录;然而,在自然感染中,基线或动力学信息难以标准化。在这里,我们分析了在用部分减毒的rDEN 2 Δ30攻击病毒感染之前、期间和之后人体中的宿主免疫转录组应答(ClinicalTrials.gov NCT 02021968)。包括I型干扰素和病毒限制性途径在内的炎性基因在DENV 2病毒血症期间被诱导,并在病毒清除后恢复至基线,而包括骨髓、迁移、体液和生长因子免疫调节因子途径在内的其他基因在病毒血症后以非基线水平存在。此外,感染前基线基因表达可用于预测rDEN 2 Δ30诱导的免疫应答和皮疹的发展。我们的研究结果表明,轻度rDEN 2 Δ30感染具有独特的免疫学特征,并为表征原发性DENV感染提供了新的潜在生物标志物。登革病毒引起一系列炎症病理,但了解人类感染期间感染的关键阶段一直具有挑战性。在这里,作者目前的免疫转录组学的变化,在急性和清除阶段的登革热病毒血清2型人类攻击模型。
About 20–25% of dengue virus (DENV) infections become symptomatic ranging from self-limiting fever to shock. Immune gene expression changes during progression to severe dengue have been documented in hospitalized patients; however, baseline or kinetic information is difficult to standardize in natural infection. Here we profile the host immunotranscriptome response in humans before, during, and after infection with a partially attenuated rDEN2Δ30 challenge virus (ClinicalTrials.gov NCT02021968). Inflammatory genes including type I interferon and viral restriction pathways are induced during DENV2 viremia and return to baseline after viral clearance, while others including myeloid, migratory, humoral, and growth factor immune regulation factors pathways are found at non-baseline levels post-viremia. Furthermore, pre-infection baseline gene expression is useful to predict rDEN2Δ30-induced immune responses and the development of rash. Our results suggest a distinct immunological profile for mild rDEN2Δ30 infection and offer new potential biomarkers for characterizing primary DENV infection. Dengue virus causes a range of inflammatory pathology but understanding critical phases of the infection during human infection has been challenging. Here the author’s present immunotranscriptomic changes during the acute and clearance phases of a dengue virus serotype 2 human challenge model.
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