Kaur Ashneet, Krishnan Viswanathan V
Department of Biology, California State University, Fresno, CA 93740, USA.
Department of Chemistry and Biochemistry, California State University, Fresno, CA 93740, USA.
PNAS Nexus. 2024 Aug 7;3(8):pgae327. doi: 10.1093/pnasnexus/pgae327. eCollection 2024 Aug.
Cytokines and chemokines are vital in maintaining a healthy state by efficiently controlling invading microbes. In addition, the dysregulation of these immune mediators can contribute to viral infection pathology. We comprehensively analyzed the profiles of host immunomodulators in response to infections with members of several virus families, particularly if the SARS-CoV-2 infection produces a unique immune profile compared with other viral infections. Multiplex microbead immunoassay results from 219 datasets with a range of viruses were curated systematically. The curated immunoassay data, obtained using Luminex technology, include 35 different viruses in 18 different viral families; this analysis also incorporated data from studies performed in 7 different cell model systems with 28 different sample types. A multivariate statistical analysis was performed with a specific focus involving many investigations (>10), which include the viral families of Coronaviridae, Orthomyxoviridae, Retroviridae, Flaviviridae, and Hantaviridae. A random forest-based classification of the profiles indicates that IL1-RA, C-X-C motif chemokine ligand 9, C-C motif chemokine ligand 4, interferon (IFN)-λ1, IFN-γ-inducing protein 10, and interleukin (IL)-27 are the top immunomodulators among human samples. Similar approaches only between Coronaviridae (COVID-19) and Orthomyxoviridae (influenza A/B) indicated that transforming growth factor-β, IFN-λ1, IL-9, and eotaxin-1 are important features. In particular, the IFN-λ1 protein was implicated as one of the significant immunomodulators differentiating viral family infection. It is evident that Coronaviridae infection, including SARS-CoV-2, induces a unique cytokine-chemokine profile and can lead to specific immunoassays for diagnosing and prognosis of viral diseases based on host immune responses. Alternatively, we can use diagnosing and prognosing. It is also essential to note that meta-analysis-based predictions must be appropriately validated before clinical implementation.
细胞因子和趋化因子在通过有效控制入侵微生物来维持健康状态方面至关重要。此外，这些免疫介质的失调会导致病毒感染病理。我们全面分析了宿主免疫调节剂对几种病毒科成员感染的反应情况，特别是与其他病毒感染相比，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染是否会产生独特的免疫特征。系统整理了来自219个包含一系列病毒的数据集的多重微珠免疫测定结果。使用Luminex技术获得的整理后的免疫测定数据包括18个不同病毒科中的35种不同病毒；该分析还纳入了在7种不同细胞模型系统中对28种不同样本类型进行研究的数据。进行了多变量统计分析，特别关注了许多调查（>10项），其中包括冠状病毒科、正粘病毒科、逆转录病毒科、黄病毒科和汉坦病毒科。基于随机森林的特征分类表明，白细胞介素1受体拮抗剂（IL1-RA）、C-X-C基序趋化因子配体9、C-C基序趋化因子配体4、干扰素（IFN）-λ1、IFN-γ诱导蛋白10和白细胞介素（IL）-27是人类样本中排名靠前的免疫调节剂。仅在冠状病毒科（COVID-19）和正粘病毒科（甲型/乙型流感）之间采用类似方法表明，转化生长因子-β、IFN-λ1、IL-9和嗜酸性粒细胞趋化因子-1是重要特征。特别是，IFN-λ1蛋白被认为是区分病毒科感染的重要免疫调节剂之一。显然，包括SARS-CoV-2在内的冠状病毒科感染会诱导独特的细胞因子-趋化因子特征，并可导致基于宿主免疫反应的病毒疾病诊断和预后的特异性免疫测定。或者，我们可以使用诊断和预后。还必须注意的是，基于荟萃分析的预测在临床实施前必须进行适当验证。
