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  • 1
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    Online Resource
    N-Acetyltransferase 9 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Proliferation by N-Terminal Acetylation of the Structural Protein GP5
    American Society for Microbiology ; 2023
    In:  Microbiology Spectrum Vol. 11, No. 1 ( 2023-02-14)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 11, No. 1 ( 2023-02-14)
    Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is a serious threat to the global swine industry. As a typical immunosuppressive virus, PRRSV has developed a variety of complex mechanisms to escape the host innate immunity. In this study, we uncovered a novel immune escape mechanism of PRRSV infection. Here, we demonstrate for the first time that the endoplasmic reticulum (ER)-resident N-acetyltransferase Nat9 is an important host restriction factor for PRRSV infection. Nat9 inhibited PRRSV proliferation in an acetyltransferase activity-dependent manner. Mechanistically, glycoprotein 5 (GP5) of PRRSV was identified as interacting with Nat9 and being N-terminally acetylated by it, which generates a GP5 degradation signal, promoting the K27-linked-ubiquitination degradation of GP5 to decrease virion assembly. Meanwhile, the expression of Nat9 was inhibited during PRRSV infection. In detail, two transcription factors, ETV5 and SP1, were screened out as the key transcription factors binding to the core promoter region of Nat9, and the PRRSV nonstructural protein 1β (Nsp1β), Nsp4, Nsp9, and nucleocapsid (N) proteins were found to interfere significantly with the expression of ETV5 and SP1, thereby regulating the transcription activity of Nat9 and inhibiting the expression of Nat9. The findings suggest that PRRSV decreases the N-terminal acetylation of GP5 to support virion assembly by inhibiting the expression of Nat9. Taken together, our findings showed that PRRSV has developed complex mechanisms to inhibit Nat9 expression and trigger virion assembly. IMPORTANCE To ensure efficient replication, a virus must hijack or regulate multiple host factors for its own benefit. Understanding virus-host interactions and the molecular mechanisms of host resistance to PRRSV infection is necessary to develop effective strategies to control PRRSV. The N-acetyltransferase Nat9 plays important roles during virus infection. Here, we demonstrate that Nat9 exhibits an antiviral effect on PRRSV proliferation. The GP5 protein of PRRSV is targeted specifically by Nat9, which mediates GP5 N-terminal acetylation and degradation via a ubiquitination-dependent proteasomal pathway. However, PRRSV manipulates the transcription factors ETV5 and SP1 to inhibit the expression of Nat9 and promote virion assembly. Thus, we report a novel function of Nat9 in PRRSV infection and elucidate a new mechanism by which PRRSV can escape the host innate immunity, which may provide novel insights for the development of antiviral drugs.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.02442-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2807133-5
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  • 2
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    Toxin-Antitoxin Systems Alter Adaptation of Mycobacterium smegmatis to Environmental Stress
    American Society for Microbiology ; 2022
    In:  Microbiology Spectrum Vol. 10, No. 6 ( 2022-12-21)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 6 ( 2022-12-21)
    Abstract: Toxin-antitoxin (TA) systems are ubiquitous genetic elements in prokaryotes, but their biological importance is poorly understood. Mycobacterium smegmatis contains eight putative TA systems. Previously, seven TAs have been studied, with five of them being verified as functional. Here, we show that Ms0251-0252 is a novel TA system in that expression of the toxin Ms0251 leads to growth inhibition that can be rescued by the antitoxin Ms0252. To investigate the functional roles of TA systems in M. smegmatis , we deleted the eight putative TA loci and assayed the mutants for resistance to various stresses. Deletion of all eight TA loci resulted in decreased survival under starvation conditions and altered fitness when exposed to environmental stresses. Furthermore, we showed that deletion of the eight TA loci decreased resistance to phage infection in Sauton medium compared with the results using 7H10 medium, suggesting that TA systems might have different contributions depending on the nutrient environment. Furthermore, we found that MazEF specifically played a dominant role in resistance to phage infection. Finally, transcriptome analysis revealed that MazEF overexpression led to differential expression of multiple genes, including those related to iron acquisition. Altogether, we demonstrate that TA systems coordinately function to allow M. smegmatis to adapt to changing environmental conditions. IMPORTANCE Toxin-antitoxin (TA) systems are mechanisms for rapid adaptation of bacteria to environmental changes. Mycobacterium smegmatis , a model bacterium for studying Mycobacterium tuberculosis , encodes eight putative TA systems. Here, we constructed an M. smegmatis mutant with deletions of all eight TA-encoding genes and evaluated the resistance of these mutants to environmental stresses. Our results showed that different TA systems have overlapping and, in some cases, opposing functions in adaptation to various stresses. We suggest that complementary TA modules may function together to regulate the bacterial stress response, enabling adaptation to changing environments. Together, this study provides key insights into the roles of TA systems in resistance to various environmental stresses, drug tolerance, and defense against phage infection.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.02815-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 3
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    Rapid Detection of Predominant SARS-CoV-2 Variants Using Multiplex High-Resolution Melting Analysis
    American Society for Microbiology ; 2023
    In:  Microbiology Spectrum Vol. 11, No. 3 ( 2023-06-15)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 11, No. 3 ( 2023-06-15)
    Abstract: Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a considerable threat to global public health. This study developed and evaluated a rapid, low-cost, expandable, and sequencing-free high-resolution melting (HRM) assay for the direct detection of SARS-CoV-2 variants. A panel of 64 common bacterial and viral pathogens that can cause respiratory tract infections was employed to evaluate our method’s specificity. Serial dilutions of viral isolates determined the sensitivity of the method. Finally, the assay’s clinical performance was assessed using 324 clinical samples with potential SARS-CoV-2 infection. Multiplex HRM analysis accurately identified SARS-CoV-2 (as confirmed with parallel reverse transcription-quantitative PCR [qRT-PCR] tests), differentiating between mutations at each marker site within approximately 2 h. For each target, the limit of detection (LOD) was lower than 10 copies/reaction (the LOD of N, G142D, R158G, Y505H, V213G, G446S, S413R, F486V, and S704L was 7.38, 9.72, 9.96, 9.96, 9.50, 7.80, 9.33, 8.25, and 8.25 copies/reaction, respectively). No cross-reactivity occurred with organisms of the specificity testing panel. In terms of variant detection, our results had a 97.9% (47/48) rate of agreement with standard Sanger sequencing. The multiplex HRM assay therefore offers a rapid and simple procedure for detecting SARS-CoV-2 variants. IMPORTANCE In the face of the current severe situation of increasing SARS-CoV-2 variants, we developed an upgraded multiplex HRM method for the predominant SARS-CoV-2 variants based on our original research. This method not only could identify the variants but also could be utilized in subsequent detection of novel variants since the assay has great performance in terms of flexibility. In summary, the upgraded multiplex HRM assay is a rapid, reliable, and economical detection method, which could better screen prevalent virus strains, monitor the epidemic situation, and help to develop measures for the prevention and control of SARS-CoV-2.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.00055-23
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
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  • 4
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    The Association between Circulating microRNAs and the Risk of Active Disease Development from Latent Tuberculosis Infection: a Nested Case-Control Study
    American Society for Microbiology ; 2022
    In:  Microbiology Spectrum Vol. 10, No. 3 ( 2022-06-29)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 3 ( 2022-06-29)
    Abstract: Tuberculosis (TB) remains one of the deadliest communicable diseases. Biomarkers predicting the risk of active disease development from latent tuberculosis infection (LTBI) are urgently needed for precise intervention. This study aimed to identify potential circulating microRNAs (miRNAs) playing such a role in Chinese population. Based on a prospective study aiming to track the development of active TB among rural residents with LTBI, the baseline levels of circulating miRNAs were retrospectively compared between those who developed TB (case group) and those age-gender matched controls remain free of TB (contraol group) during the follow-up. Agilent human miRNA microarray were used to select differently expressed circulating miRNAs and verified by subsequent real-time quantitative PCR (RT-qPCR). Six candidate miRNAs were expressed at statistically significant levels between the two groups at the baseline, as determined by microarray. Following verification among 150 study participants by RT-qPCR, the levels of hsa-miR-16-5p ( P 〈 0.001) and hsa-miR-451a ( P 〈 0.001) were found to be significantly lower in case group compared to control group. The combined areas under curves (AUCs) and precision-recall curves (PRCs) were 0.84, 0.86 and 0.85, 0.87 for hsa-miR-16-5p and hsa-miR-451a , respectively. hsa-miR-451a combined with body mass index (BMI) and prior history of TB presented the best performance, with a sensitivity of 80.82% and an acceptable specificity of 79.22%. After adjusting the two co-variables, the AUC of hsa-miR-451a was 0.78. Circulating levels of hsa-miR-451a showed potential to predict development of active TB from LTBI in a Chinese population. Further studies are warranted to verify these findings in varied study settings. IMPORTANCE Approximately a quarter of the world population are infected with M. tuberculosis and about 5% to 10% of these might develop active disease in their lifetime. Preventive treatment could effectively protect individuals at a high risk of developing active disease from LTBI, and is regarded as a critical component of End TB Strategies. Biomarkers which could accurately identify high-risk population and predict the risk of disease development are urgently needed for developing local guidelines of LTBI management and precise intervention. A nested case-control study was designed to explore possible microRNAs related with TB occurrence based on a previous prospective study, which aimed to track the development of active TB among rural residents with LTBI. The baseline circulating levels of hsa-miR-16-5p and hsa-miR-451a were significantly lower in TB cases compared to those in LTBI controls. Further receiver operator characteristic (ROC) curve analysis found that hsa-miR-451a showed considerable potential to predict the development of active TB from LTBI.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.02625-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 5
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    Online Resource
    A high sensitivity strategy of DNMT1 activity detection based on self-assembled nucleic acid probe signal amplification technique
    Elsevier BV ; 2023
    In:  Sensors and Actuators B: Chemical Vol. 385 ( 2023-06), p. 133610-
    Details
    In: Sensors and Actuators B: Chemical, Elsevier BV, Vol. 385 ( 2023-06), p. 133610-
    Type of Medium: Online Resource
    ISSN: 0925-4005
    URL: Article
    DOI: 10.1016/j.snb.2023.133610
    RVK:
    ZG 1100
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1500731-5
    detail.hit.zdb_id: 1021505-0
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  • 6
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    SNX27-mediated endocytic recycling of GLUT1 is suppressed by SARS-CoV-2 spike, possibly explaining neuromuscular disorders in patients with COVID-19
    Elsevier BV ; 2022
    In:  Journal of Infection Vol. 85, No. 4 ( 2022-10), p. e116-e118
    Details
    In: Journal of Infection, Elsevier BV, Vol. 85, No. 4 ( 2022-10), p. e116-e118
    Type of Medium: Online Resource
    ISSN: 0163-4453
    URL: Article
    DOI: 10.1016/j.jinf.2022.06.021
    RVK:
    XA 54270
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2012883-6
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  • 7
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    Relationship between DNA Methylation Profiles and Active Tuberculosis Development from Latent Infection: a Pilot Study in Nested Case-Control Design
    American Society for Microbiology ; 2022
    In:  Microbiology Spectrum Vol. 10, No. 3 ( 2022-06-29)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 3 ( 2022-06-29)
    Abstract: Individuals with latent tuberculosis infection (LTBI) were regarded as an enormous reservoir of cases with active tuberculosis (TB). To strengthen LTBI management, biomarkers and tools are urgently required for identifying and ruling out active TB in a fast and effective way. Based on an open-label randomized controlled trial aiming to explore short-course LTBI treatment regimens, DNA methylation profiles were retrospectively detected to explore potential biomarkers, which could discriminate active TB from LTBI. The Infinium MethylationEPIC BeadChip array was used to analyze genomewide DNA methylation levels for 15 persons with LTBI who later developed active TB and for 15 LTBI controls who stayed healthy. The differentially methylated CpGs (dmCpGs) located in the promoter regions pre- and post-TB diagnosis were selected ( P   〈  0.05 and |Δβ| 〉 0.10) and evaluated by receiver operating characteristic (ROC) analysis. Eight dmCpGs were identified to be associated with TB occurrence; six were located in hypermethylated genes (cg02493602, cg02206980, cg02214623, cg12159502, cg14593639, and cg25764570), and two were located in hypomethylated genes (cg02781074 and cg12321798). ROC analysis indicated that the area under curve (AUC) of these eight dmCpGs ranged from 0.72 to 0.84. Given 90% sensitivity, the specificity was highest for cg14593639 at 66.67%. The combination analysis indicated that “cg02206980 + cg02214623 + cg12159502 + cg12321798” showed the best performance, with an AUC of 0.88 (95% confidence interval [CI]: 0.72, 0.97), a sensitivity of 93.33% (95% CI: 70.18%, 99.66%), and a specificity of 86.67% (95% CI: 62.12%, 97.63%). Our preliminary results indicate the potential value of the DNA methylation level as a diagnostic biomarker for discriminating active disease in LTBI testing. This finding requires further verification in independent populations with large sample sizes. IMPORTANCE Approximately a quarter of the world population had been infected with Mycobacterium tuberculosis , and about 5 to 10% of these individuals might develop active disease in their lifetimes. As a critical component of the “end TB strategies,” preventive treatment was shown to protect 60 to 90% of high-risk LTBIs from developing active disease. Developing new TB screening tools based on blood-based biomarkers, which could identify and rule out active TB from LTBI, are prerequisite before initialing intervention. We tried to explore potential DNA methylation diagnostic biomarkers through retrospectively detected DNA methylation profiles pre- and post-TB diagnosis. Eight dmCpGs were identified, and the combination of “cg02206980 + cg02214623 + cg12159502 + cg12321798” showed a sensitivity of 93.33% and a specificity of 86.67%. The preliminary results provided new insight into detecting the DNA methylation level as a potential tool to distinguish TB from LTBI.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.00586-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 8
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    Fatty Acid Synthase Promotes the Palmitoylation of Chikungunya Virus nsP1
    American Society for Microbiology ; 2019
    In:  Journal of Virology Vol. 93, No. 3 ( 2019-02)
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 93, No. 3 ( 2019-02)
    Abstract: Chikungunya virus (CHIKV) is transmitted to people by mosquitoes, and CHIKV infection causes fever and joint pain. Fatty acid synthase (FASN) has been identified as a proviral factor for CHIKV. How FASN participates in CHIKV replication remains to be elucidated. In this study, we demonstrated that palmitic acid (PA) can restore the suppression of CHIKV replication by FASN inhibitors. The palmitoylation and plasma membrane localization of CHIKV nsP1 were reduced by FASN inhibitors. Triple mutation of Cys417, Cys418, and Cys419 in nsP1 blocked its palmitoylation and severely disrupted CHIKV replication. Furthermore, two zinc finger DHHC domain-containing palmitoyltransferases (ZDHHCs), ZDHHC2 and ZDHHC19, promoted nsP1 palmitoylation and CHIKV replication. Our results not only identified the key enzymes for the palmitoylation of nsP1 but also provided mechanistic insights into the roles of FASN in CHIKV replication. IMPORTANCE S-palmitoylation is an important form of lipid posttranslational modification, which affects the function of proteins by regulating their transport, stability, and localization. Previous studies have shown that FASN is critical for CHIKV replication; however, the mechanism for this function of FASN remains unknown. The key zinc finger DHHC domain-containing palmitoyltransferases involved in the palmitoylation of nsP1 are not clear. We demonstrated that FASN promoted CHIKV replication through nsP1 palmitoylation. ZDHHC2 and ZDHHC19 were identified as the major enzymes for nsP1 palmitoylation. Since nsP1 proteins are conserved in alphaviruses, our results highlight the mechanisms by which alphavirus nsP1 is palmitoylated.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01747-18
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1495529-5
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  • 9
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    Intraviral interactome of Chikungunya virus reveals the homo-oligomerization and palmitoylation of structural protein TF
    Elsevier BV ; 2019
    In:  Biochemical and Biophysical Research Communications Vol. 513, No. 4 ( 2019-06), p. 919-924
    Details
    In: Biochemical and Biophysical Research Communications, Elsevier BV, Vol. 513, No. 4 ( 2019-06), p. 919-924
    Type of Medium: Online Resource
    ISSN: 0006-291X
    URL: Article
    DOI: 10.1016/j.bbrc.2019.04.098
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 1461396-7
    SSG: 12
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  • 10
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    A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-06-21)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-06-21)
    Abstract: Hepatitis C virus (HCV) entry into hepatocytes is a multistep process that represents a promising target for antiviral intervention. The viral envelope protein E1E2 plays a critical role in HCV entry. In this study, we sought to identify peptide inhibitors of HCV by screening a library of overlapping peptides covering E1E2. Screening the peptide library identified several novel anti-HCV peptides. Four peptides from glycoprotein E2 were selected for further investigation. The 50% effective dose (ED50) was approximately 5 nM for each peptide. Our data indicated that these peptides inhibited HCV entry at the post-attachment step. Moreover, these peptides blocked cell-to-cell transmission of HCVcc and had broad-spectrum antiviral effects on HCVcc. These peptides exhibited combination inhibitory effects on HCVcc infection when combined with IFN-α2b or anti-CD81 antibody. Interestingly, we observed that E2-42 associated with E1 and E2. Our results indicate that E2-42 inhibits HCV entry via E1 and E2. These findings suggest a new avenue for HCV therapeutic development.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-017-04274-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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