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Article ; Online: Enhancement of SARS-CoV-2 vaccine-induced immunity by a Toll-like receptor 7 agonist adjuvant

Gen Li / Meixing Yu / Qiong Ke / Jing Sun / Yanwen Peng / Chuanfeng Xiong / Olivia Monteiro / Jincun Zhao / Andy P. Xiang

Signal Transduction and Targeted Therapy, Vol 8, Iss 1, Pp 1-

2023 Volume 4

Keywords	Medicine ; R ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Aptamer blocking S-TLR4 interaction selectively inhibits SARS-CoV-2 induced inflammation

Gang Yang / Shengnan Zhang / Yuchun Wang / Ling Li / Yu Li / Deyu Yuan / Fatao Luo / Jincun Zhao / Xu Song / Yongyun Zhao

Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-

2022 Volume 3

Keywords	Medicine ; R ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dynamic immune landscape in vaccinated-BA.5-XBB.1.9.1 reinfections revealed a 5-month protection-duration against XBB infection and a shift in immune imprintingResearch in context

Tingting Cui / Xiaoling Su / Jing Sun / Siyi Liu / Mingzhu Huang / Weidong Li / Chengna Luo / Li Cheng / Rui Wei / Tao Song / Xi Sun / Qi Luo / Juan Li / Jie Su / Shidong Deng / Jincun Zhao / Zhuxiang Zhao / Nanshan Zhong / Zhongfang Wang

EBioMedicine, Vol 99, Iss , Pp 104903- (2024)

1481

Abstract: Summary: Background: The impact of previous vaccination on protective immunity, duration, and immune imprinting in the context of BA.5-XBB.1.9.1 reinfection remains unknown. Methods: Based on a 2-year longitudinal cohort from vaccination, BA.5 infection ... ...

Abstract	Summary: Background: The impact of previous vaccination on protective immunity, duration, and immune imprinting in the context of BA.5-XBB.1.9.1 reinfection remains unknown. Methods: Based on a 2-year longitudinal cohort from vaccination, BA.5 infection and XBB reinfection, several immune effectors, including neutralizing antibodies (Nabs), antibody-dependent cellular cytotoxicity (ADCC), virus-specific T cell immunity were measured to investigate the impact of previous vaccination on host immunity induced by BA.5 breakthrough infection and BA.5-XBB.1.9.1 reinfection. Findings: In absence of BA.5 Nabs, plasma collected 3 months after receiving three doses of inactivated vaccine (I-I-I) showed high ADCC that protected hACE2-K18 mice from fatality and significantly reduced viral load in the lungs and brain upon BA.5 challenge, compared to plasma collected 12 months after I-I-I. Nabs against XBB.1.9.1 induced by BA.5 breakthrough infection were low at day 14 and decreased to a GMT of 10 at 4 months and 28% (9/32) had GMT ≤4, among whom 67% (6/9) were reinfected with XBB.1.9.1 within 1 month. However, 63% (20/32) were not reinfected with XBB.1.9.1 at 5 months post BA.5 infection. Interestingly, XBB.1.9.1 reinfection increased Nabs against XBB.1.9.1 by 24.5-fold at 14 days post-reinfection, which was much higher than that against BA.5 (7.3-fold) and WT (4.5-fold), indicating an immune imprinting shifting from WT to XBB antigenic side. Interpretation: Overall, I-I-I can provide protection against BA.5 infection and elicit rapid immune response upon BA.5 infection. Furthermore, BA.5 breakthrough infection effectively protects against XBB.1.9.1 lasting more than 5 months, and XBB.1.9.1 reinfection results in immune imprinting shifting from WT antigen induced by previous vaccination to the new XBB.1.9.1 antigen. These findings strongly suggest that future vaccines should target variant strain antigens, replacing prototype strain antigens. Funding: This study was supported by R&D Program of Guangzhou National ...
Keywords	SARS-CoV-2 ; Vaccinated-BA.5-XBB.1.9.1 reinfections ; Immune imprinting ; Protection-duration ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir

Yan Zhao / Jing Sun / Yunfei Li / Zhengxuan Li / Yu Xie / Ruoqing Feng / Jincun Zhao / Yuhui Hu

iScience, Vol 24, Iss 8, Pp 102857- (2021)

2021

Abstract: Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive single-stranded RNA virus, causes the coronavirus disease 19 pandemic. During the viral replication and transcription, the RNA-dependent RNA polymerase “jumps” along the ... ...

Abstract	Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive single-stranded RNA virus, causes the coronavirus disease 19 pandemic. During the viral replication and transcription, the RNA-dependent RNA polymerase “jumps” along the genome template, resulting in discontinuous negative-stranded transcripts. Although the sense-mRNA architectures of SARS-CoV-2 were reported, its negative strand was unexplored. Here, we deeply sequenced both strands of RNA and found SARS-CoV-2 transcription is strongly biased to form the sense strand with variable transcription efficiency for different genes. During negative strand synthesis, numerous non-canonical fusion transcripts are also formed, driven by 3-15 nt sequence homology scattered along the genome but more prone to be inhibited by SARS-CoV-2 RNA polymerase inhibitor remdesivir. The drug also represses more of the negative than the positive strand synthesis as supported by a mathematic simulation model and experimental quantifications. Overall, this study opens new sights into SARS-CoV-2 biogenesis and may facilitate the antiviral vaccine development and drug design.
Keywords	virology ; mathematical biosciences ; systems biology ; Science ; Q
Subject code	572
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sensitization of Non-permissive Laboratory Mice to SARS-CoV-2 with a Replication-Deficient Adenovirus Expressing Human ACE2

Lok-Yin Roy Wong / Kun Li / Jing Sun / Zhen Zhuang / Jincun Zhao / Paul B. McCray, Jr. / Stanley Perlman

STAR Protocols, Vol 1, Iss 3, Pp 100169- (2020)

2020

Abstract: Summary: Common laboratory mice such as BALB/c and C57BL/6 mice are not permissive to SARS-CoV2 infection. Sensitization of laboratory mice with Adenovirus expressing human ACE2 (Ad5-hACE2) provides a rapid model for testing viral intervention in vivo. ... ...

Abstract	Summary: Common laboratory mice such as BALB/c and C57BL/6 mice are not permissive to SARS-CoV2 infection. Sensitization of laboratory mice with Adenovirus expressing human ACE2 (Ad5-hACE2) provides a rapid model for testing viral intervention in vivo. Despite the lack of lethal outcome, Ad5-hACE2-sensitized mice show 20% weight loss on average upon viral challenge with infectious virus being detected at the site of sensitization. This protocol describes the sensitization and subsequent infection of common laboratory mice for use in testing anti-viral interventions.For complete details on the use and execution of this protocol, please refer to Sun et al. (2020).
Keywords	Immunology ; Model Organisms ; Science (General) ; Q1-390
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19

Fei Xiao / Jing Sun / Yonghao Xu / Fang Li / Xiaofang Huang / Heying Li / Jingxian Zhao / Jicheng Huang / Jincun Zhao

Emerging Infectious Diseases, Vol 26, Iss 8, Pp 1920-

2020 Volume 1922

Abstract: Severe acute respiratory syndrome coronavirus 2 was isolated from feces of a patient in China with coronavirus disease who died. Confirmation of infectious virus in feces affirms the potential for fecal–oral or fecal–respiratory transmission and warrants ...

Abstract	Severe acute respiratory syndrome coronavirus 2 was isolated from feces of a patient in China with coronavirus disease who died. Confirmation of infectious virus in feces affirms the potential for fecal–oral or fecal–respiratory transmission and warrants further study.
Keywords	severe acute respiratory syndrome coronavirus 2 ; SARS-CoV-2 ; viruses ; coronavirus ; coronavirus disease ; COVID-19 ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Virus-specific regulatory T cells ameliorate encephalitis by repressing effector T cell functions from priming to effector stages.

Jingxian Zhao / Jincun Zhao / Stanley Perlman

PLoS Pathogens, Vol 10, Iss 8, p e

2014 Volume 1004279

Abstract: Several studies have demonstrated the presence of pathogen-specific Foxp3+ CD4 regulatory T cells (Treg) in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive ... ...

Abstract	Several studies have demonstrated the presence of pathogen-specific Foxp3+ CD4 regulatory T cells (Treg) in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently showed the presence of both epitope M133-specific Tregs (M133 Treg) and conventional CD4 T cells (M133 Tconv) in the brains of mice with coronavirus-induced encephalitis. Here, we provide new insights into the interactions between pathogenic Tconv and Tregs responding to the same epitope. M133 Tregs inhibited the proliferation but not initial activation of M133 Tconv in draining lymph nodes (DLN). Further, M133 Tregs inhibited migration of M133 Tconv from the DLN. In addition, M133 Tregs diminished microglia activation and decreased the number and function of Tconv in the infected brain. Thus, virus-specific Tregs inhibited pathogenic CD4 T cell responses during priming and effector stages, particularly those recognizing cognate antigen, and decreased mortality and morbidity without affecting virus clearance. These cells are more suppressive than bulk Tregs and provide a targeted approach to ameliorating immunopathological disease in infectious settings.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2014-08-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic and pathogenicity diversity of dengue virus type 2 strains circulating in Guangdong, China

Lu Zhang / Lingzhai Zhao / Zhaoyong Zhang / Wenxin Hong / Jian Wang / Shuang Qiu / Huiqin Yang / Mian Gan / Jing Sun / Jingxian Zhao / Yanqun Wang / Jincun Zhao / Fuchun Zhang

Biosafety and Health, Vol 3, Iss 6, Pp 333-

2021 Volume 342

Abstract: Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus (DENV). DENV causes a febrile illness, severe forms including hemorrhagic fevers and shock with fatalities in humans. DENV-2 is ... ...

Abstract	Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus (DENV). DENV causes a febrile illness, severe forms including hemorrhagic fevers and shock with fatalities in humans. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 strains from Guangdong, China, have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo. A total of 22 patients tested to be DENV-2 positive and were enrolled in this study, 22 complete genomes were obtained by virus isolation and high-throughput sequencing. Phylogenetic and single amino polymorphism (SAP) analysis indicated that two major subgenotypes (A and C) of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018. The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains, including endemic genotype and imported genotype. It alerted the risk of cross-border transmission of DENV. A significant difference in replication rate was observed in C6/36 between different DENV-2 strains, although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles. DENV-2 subgenotypes (A and C) replicated efficiently in IFNAR−/− C57BL/6 mice, and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group. DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo, indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.
Keywords	DENV-2 ; Genetic ; Pathogenicity ; Diversity ; Infectious and parasitic diseases ; RC109-216 ; Public aspects of medicine ; RA1-1270
Subject code	570
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A novel luciferase immunosorbent assay performs better than a commercial enzyme-linked immunosorbent assay to detect MERS-CoV specific IgG in humans and animals

Wenling Wang / Tianyu Wang / Yao Deng / Peihua Niu / Ruhan A / Jincun Zhao / Malik Peiris / Shixing Tang / Wenjie Tan

Biosafety and Health, Vol 1, Iss 3, Pp 134-

2019 Volume 143

Abstract: The Middle East respiratory syndrome (MERS) is a lethal zoonosis caused by MERS coronavirus (MERS-CoV) and poses a significant threat to public health worldwide. Therefore, a rapid, sensitive, and specific serologic test for detecting anti-MERS-CoV ... ...

Abstract	The Middle East respiratory syndrome (MERS) is a lethal zoonosis caused by MERS coronavirus (MERS-CoV) and poses a significant threat to public health worldwide. Therefore, a rapid, sensitive, and specific serologic test for detecting anti-MERS-CoV antibodies in both humans and animals is urgently needed for the successful management of this illness. Here, we evaluated various novel luciferase immunosorbent assays (LISA) based on nucleocapsid protein (NP) as well as fragments derived from spike protein (S) including subunit 1 (S1), N terminal domain (NTD), receptor-binding domain (RBD) and subunit 2 (S2) of S for the detection of MERS-CoV-specific IgG. Fusion proteins, including nanoluciferase (NLuc) and various fragments derived from the NP or S protein of MERS-CoV, were expressed in human embryonic kidney 293 T cells. LISAs that detected anti-MERS-CoV IgG were further developed using cell lysates expressing various fusion proteins. Panels of human or animal samples infected with MERS-CoV were used to analyze the sensitivity and specificity of various LISAs in reference to a MERS-CoV RT-PCR, commercial S1-based ELISA, and pseudovirus particle neutralization test (ppNT). Our results showed that the S1-, RBD-, and NP-LISAs were more sensitive than the NTD- and S2-LISAs for the detection of anti-MERS-CoV IgG. Furthermore, the S1-, RBD-, and NP-LISAs were more sensitive (by at least 16-fold) than the commercially available S1-ELISA. Moreover, the S1-, RBD-, and NP-LISA specifically recognized anti-MERS-CoV IgG and did not cross-react with samples derived from other human CoV (OC43, 229E, HKU1, NL63)-infected patients. More importantly, these LISAs proved their applicability and reliability for detecting anti-MERS-CoV IgG in samples from camels, monkeys, and mice, among which the RBD-LISA exhibited excellent performance. The results of this study suggest that the novel MERS-CoV RBD- and S1- LISAs are highly effective platforms for the rapid and sensitive detection of anti-MERS-CoV IgG in human and animal samples. ...
Keywords	Luciferase immunosorbent assay (LISA) ; MERS-CoV ; Serological IgG detection ; Samples of humans and animals ; Infectious and parasitic diseases ; RC109-216 ; Public aspects of medicine ; RA1-1270
Subject code	570
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation

Yaoxing Wu / Ling Ma / Sihui Cai / Zhen Zhuang / Zhiyao Zhao / Shouheng Jin / Weihong Xie / Lingli Zhou / Lei Zhang / Jincun Zhao / Jun Cui

Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract The ongoing 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat. The severity and mortality of COVID-19 are associated with virus-induced dysfunctional ... ...

Abstract	Abstract The ongoing 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat. The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms. However, the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown. Here, we demonstrate that SARS-CoV-2 nucleocapsid (N) protein, the major structural protein of the virion, promotes the virus-triggered activation of NF-κB signaling. After binding to viral RNA, N protein robustly undergoes liquid–liquid phase separation (LLPS), which recruits TAK1 and IKK complex, the key kinases of NF-κB signaling, to enhance NF-κB activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-κB activation. These results suggest that LLPS of N protein provides a platform to induce NF-κB hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.
Keywords	Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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