Single-cell landscape of peripheral immune responses to fatal SFTS

Li, Hao; Li, Xiaokun; Lv, Shou-Ming; Peng, Xue-Fang; Cui, Ning; Yang, Tong; Yang, Zhen‐Dong; Yuan, Chun; Yuan, Yang; Yao, Jiaying; Yuan, Zan; Li, Jiachen; Ye, Xiao-Lei; Zhang, Xiao-Ai; Zhu, Shu; Peng, Ke; Liu, Wei

doi:10.1016/j.celrep.2021.110039

Cited by 21 publications

(22 citation statements)

References 82 publications

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“…Further analysis of viral loads and viremia duration revealed no potential biological significance from more rapid viral replication for the clade IV. Interestingly, a pronounced inflammation was produced from the patients and PBMCs with clade IV infection or inoculation, in agreement with the previously determined association between severe SFTS and uncontrolled inflammatory response, which similarly involved elevated levels of CXCL10, granulocyte-CSF (G-CSF), IL-6, IL-10, IL-1β, MIP-1α, and MCP-1 in patients with the severe or fatal disease [ 17 , 27 , 28 ]. The hyper-inflammation response in SFTSV infection might disturb the coagulation system and promote the development of DIC, which underpins the causative correlation between clade IV and higher odds of death from SFTS [ 3 , 27 , 29 ].…”

Section: Discussionsupporting

confidence: 86%

Effect of genomic variations in severe fever with thrombocytopenia syndrome virus on the disease lethality

Dai

Peng

et al. 2022

Emerging Microbes & Infections

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Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1β, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.

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Section: Discussionsupporting

confidence: 86%

Effect of genomic variations in severe fever with thrombocytopenia syndrome virus on the disease lethality

Dai

Peng

et al. 2022

Emerging Microbes & Infections

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“…Libraries were sequenced with a 2 × 100-bp paired-end protocol on a Novaseq-6000 platform (Illumina, San Diego, CA, USA) to generate at least 40,000 read pairs per cell. The sequencing depth recommended by the manufacturer for the 3′ Gene Expression library is a minimum of 20,000 read pairs per cell, and values in the range of 20,000 to 50,000 read pairs per cell are commonly used in the field [ 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

Single-cell RNA sequencing of mitotic-arrested prospermatogonia with DAZL::GFP chickens and revealing unique epigenetic reprogramming of chickens

Choi

Jung

Rengaraj

et al. 2022

J Animal Sci Biotechnol

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Background Germ cell mitotic arrest is conserved in many vertebrates, including birds, although the time of entry or exit into quiescence phase differs. Mitotic arrest is essential for the normal differentiation of male germ cells into spermatogonia and accompanies epigenetic reprogramming and meiosis inhibition from embryonic development to post-hatch. However, mitotic arrest was not well studied in chickens because of the difficulty in obtaining pure germ cells from relevant developmental stage. Results We performed single-cell RNA sequencing to investigate transcriptional dynamics of male germ cells during mitotic arrest in DAZL::GFP chickens. Using differentially expressed gene analysis and K-means clustering to analyze cells at different developmental stages (E12, E16, and hatch), we found that metabolic and signaling pathways were regulated, and that the epigenome was reprogrammed during mitotic arrest. In particular, we found that histone H3K9 and H3K14 acetylation (by HDAC2) and DNA demethylation (by DNMT3B and HELLS) led to a transcriptionally permissive chromatin state. Furthermore, we found that global DNA demethylation occurred gradually after the onset of mitotic arrest, indicating that the epigenetic-reprogramming schedule of the chicken genome differs from that of the mammalian genome. DNA hypomethylation persisted after hatching, and methylation was slowly re-established 3 weeks later. Conclusions We found a unique epigenetic-reprogramming schedule of mitotic-arrested chicken prospermatogonia and prolonged hypomethylation after hatching. This will provide a foundation for understanding the process of germ-cell epigenetic regulation in several species for which this process is not clearly described. Our findings on the biological processes related to sex-specific differentiation of prospermatogonia could help studying germline development in vitro more elaborately.

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“…Monocytes also participate in regulating the function of plasma cell-like DCs (pDCs), and TNF-α secreted by pDCs plays an important role in the antiviral immune response ( 22 , 23 ). It has been found that monocytes may be one of the main target cells of SFTSV infection ( 23 – 25 ). Decreased numbers and dysfunction of monocytes in patients with acute SFTS are related to the severity of the disease ( 23 ).At the early stage of fatal SFTSV infection, Song et al.…”

Section: Innate Immune Evasion By Sftsvmentioning

confidence: 99%

“…Monocytes also participate in regulating the function of plasma cell-like DCs (pDCs), and TNF-a secreted by pDCs plays an important role in the antiviral immune response (22,23). It has been found that monocytes may be one of the main target cells of SFTSV infection (23)(24)(25).…”

Section: Attenuated Function Of Mononuclear Cells and Dcs By Sftsv In...mentioning

confidence: 99%

Immune escape mechanisms of severe fever with thrombocytopenia syndrome virus

Wang

Zhu

et al. 2022

Front. Immunol.

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Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), poses a serious threat to global public health, with high fatalities and an increasing prevalence. As effective therapies and prevention strategies are limited, there is an urgent need to elucidate the pathogenesis of SFTS. SFTSV has evolved several mechanisms to escape from host immunity. In this review, we summarize the mechanisms through which SFTSV escapes host immune responses, including the inhibition of innate immunity and evasion of adaptive immunity. Understanding the pathogenesis of SFTS will aid in the development of new strategies for the treatment of this disease.

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Single-cell landscape of peripheral immune responses to fatal SFTS

Cited by 21 publications

References 82 publications

Effect of genomic variations in severe fever with thrombocytopenia syndrome virus on the disease lethality

Effect of genomic variations in severe fever with thrombocytopenia syndrome virus on the disease lethality

Single-cell RNA sequencing of mitotic-arrested prospermatogonia with DAZL::GFP chickens and revealing unique epigenetic reprogramming of chickens

Immune escape mechanisms of severe fever with thrombocytopenia syndrome virus

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