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Artikel ; Online: Molecular Beacons Allow Specific RT-LAMP Detection of B.1.1.7 Variant SARS-CoV-2.

Sherrill-Mix, Scott / Van Duyne, Gregory D / Bushman, Frederic D

Journal of biomolecular techniques : JBT

2022 Band 32, Heft 3, Seite(n) 98–101

Abstract: Over the course of the coronavirus disease 2019 (COVID-19) pandemic, several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic variants of concern have appeared and spread throughout the world. Detection and identification of these ... ...

Abstract	Over the course of the coronavirus disease 2019 (COVID-19) pandemic, several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic variants of concern have appeared and spread throughout the world. Detection and identification of these variants are important to understanding and controlling their rapid spread. Current detection methods for a particularly concerning variant, B.1.1.7, require expensive quantitative PCR machines and depend on the absence of a signal rather than a positive indicator of variant presence. Here we report an assay using a pair of molecular beacons combined with reverse transcription loop mediated amplification to allow isothermal amplification from saliva to specifically detect B.1.1.7 and other variants that contain a characteristic deletion in the gene encoding the viral spike protein. This assay is specific and affordable and allows multiplexing with other SARS-CoV-2 loop-mediated amplification primer sets.
Mesh-Begriff(e)	COVID-19 ; COVID-19 Testing ; Humans ; Molecular Diagnostic Techniques ; Nucleic Acid Amplification Techniques ; RNA, Viral/genetics ; SARS-CoV-2 ; Sensitivity and Specificity
Chemische Substanzen	RNA, Viral
Sprache	Englisch
Erscheinungsdatum	2022-01-13
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2116011-9
ISSN	1943-4731 ; 1943-4731
ISSN (online)	1943-4731
ISSN	1943-4731
DOI	10.7171/jbt.21-3203-004
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Virome in immunodeficiency: what we know currently.

Wang, Hu / Xu, Siqi / Li, Shuang / Su, Bin / Sherrill-Mix, Scott / Liang, Guanxiang

Chinese medical journal

2023 Band 136, Heft 22, Seite(n) 2647–2657

Abstract: Abstract: Over the past few years, the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter ... ...

Abstract	Abstract: Over the past few years, the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases. This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status. By surveying the latest literature, we present a detailed overview of virome alterations observed in various immunodeficiency conditions. We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals. Furthermore, this review explores the clinical relevance of virome studies in the context of immunodeficiency, highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.
Mesh-Begriff(e)	Humans ; Viruses ; Virome ; Microbiota ; Immunologic Deficiency Syndromes
Sprache	Englisch
Erscheinungsdatum	2023-11-01
Erscheinungsland	China
Dokumenttyp	Review ; Journal Article
ZDB-ID	127089-8
ISSN	2542-5641 ; 0366-6999 ; 1002-0187
ISSN (online)	2542-5641
ISSN	0366-6999 ; 1002-0187
DOI	10.1097/CM9.0000000000002899
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: A cone-beam computed tomographic evaluation of alveolar bone dimensional changes and the periodontal limits of mandibular incisor advancement in skeletal Class II patients.

Matsumoto, Kensuke / Sherrill-Mix, Scott / Boucher, Normand / Tanna, Nipul

The Angle orthodontist

2020 Band 90, Heft 3, Seite(n) 330–338

Abstract: Objectives: To evaluate the presence of dehiscences and changes in alveolar bone height and width in the area of the mandibular central incisors pre- and post-orthodontic treatment.: Materials and methods: In 60 skeletal Class II patients, cone-beam ... ...

Abstract	Objectives: To evaluate the presence of dehiscences and changes in alveolar bone height and width in the area of the mandibular central incisors pre- and post-orthodontic treatment. Materials and methods: In 60 skeletal Class II patients, cone-beam computed tomographic (CBCT) images were obtained and the patients were divided into four groups based on the presence of dehiscences at pre- and post-orthodontic treatment. The alveolar bone height and width were measured on CBCT in cross section along the long axis of the teeth. Lateral cephalograms were analyzed. Results: The changes in L1-NB and IMPA appeared to be correlated with vertical bone loss and dehiscence. Alveolar bone height appeared to follow a segmented relationship with these two variables, with changes below a threshold (L1-NB = 0.71 mm, IMPA = 3.02°) having relatively minimal or no effect on bone loss but with changes beyond the threshold correlated with extensive bone loss. Similarly, increases in L1-NB or IMPA correlated with decreases in alveolar bone width (L1-NB: -0.25 mm/mm, IMPA: -0.07 mm/°) and increased the probability of developing dehiscences, with an estimated 50% probability of vertical bone loss at a L1-NB change of 2.00 mm or, equivalently, an IMPA change of 8.02° was estimated. Conclusions: When treating skeletal Class II patients, the limits of incisor proclination/protraction are less than previously thought. To prevent undesired periodontal outcomes, careful three-dimensional diagnosis is advisable. Furthermore, when excessive protrusion and/or proclination is planned, additional treatment modalities, including orthognathic surgery, tooth extraction, and corticotomy with bone graft, should be considered.
Mesh-Begriff(e)	Alveolar Process/diagnostic imaging ; Cephalometry ; Cone-Beam Computed Tomography ; Humans ; Incisor/diagnostic imaging ; Malocclusion, Angle Class III ; Mandible/diagnostic imaging
Sprache	Englisch
Erscheinungsdatum	2020-12-23
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	390289-4
ISSN	1945-7103 ; 0003-3219
ISSN (online)	1945-7103
ISSN	0003-3219
DOI	10.2319/080219-510.1
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Molecular beacons allow specific RT-LAMP detection of B.1.1.7 variant SARS-CoV-2

Sherrill-Mix, Scott / Van Duyne, Gregory D / Bushman, Frederic D

medRxiv

Abstract: Over the course of the COVID-19 pandemic, several SARS-CoV-2 genetic variants of concern have appeared and spread throughout the world. Detection and identification of these variants is important to understanding and controlling their rapid spread. ... ...

Abstract	Over the course of the COVID-19 pandemic, several SARS-CoV-2 genetic variants of concern have appeared and spread throughout the world. Detection and identification of these variants is important to understanding and controlling their rapid spread. Current detection methods for a particularly concerning variant, B.1.1.7, require expensive qPCR machines and depend on the absence of a signal rather than a positive indicator of variant presence. Here we report an assay using a pair of molecular beacons paired with reverse transcription loop mediated amplification to allow isothermal amplification from saliva to specifically detect B.1.1.7 and other variants which contain a characteristic deletion in the gene encoding the viral spike protein. This assay is specific, affordable and allows multiplexing with other SARS-CoV-2 LAMP primer sets.
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2021-03-26
Verlag	Cold Spring Harbor Laboratory Press
Dokumenttyp	Artikel ; Online
DOI	10.1101/2021.03.25.21254356
Datenquelle	COVID19

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Artikel ; Online: Virus structures constrain transmission modes.

Bushman, Frederic D / McCormick, Kevin / Sherrill-Mix, Scott

Nature microbiology

2019 Band 4, Heft 11, Seite(n) 1778–1780

Abstract: Here we investigate links between the structures of viruses and routes of transmission. Viruses show a wide range of different structures, and the transmission of viruses between vertebrate hosts can take place through many different routes. We compiled ... ...

Abstract	Here we investigate links between the structures of viruses and routes of transmission. Viruses show a wide range of different structures, and the transmission of viruses between vertebrate hosts can take place through many different routes. We compiled a database of 243 virus-host combinations and report a statistical analysis that documents the associations between structures and routes of transmission-for example, viruses that are transmitted by the faecal-oral mode of infection are rarely enclosed in a lipid envelope.
Mesh-Begriff(e)	Animals ; Cats ; Cattle ; Chickens ; Dogs ; Feces/virology ; Genome, Viral ; Horses ; Humans ; Mouth/virology ; Swine ; Vertebrates/virology ; Viral Structures ; Virus Diseases/transmission ; Virus Diseases/veterinary ; Viruses/chemistry ; Viruses/genetics
Sprache	Englisch
Erscheinungsdatum	2019-07-29
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-019-0523-5
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.

Tanneti, Nikhila S / Patel, Anant K / Tan, Li Hui / Marques, Andrew D / Perera, Ranawaka A P M / Sherrill-Mix, Scott / Kelly, Brendan J / Renner, David M / Collman, Ronald G / Rodino, Kyle / Lee, Carole / Bushman, Frederic D / Cohen, Noam A / Weiss, Susan R

mBio

2024 Band 15, Heft 4, Seite(n) e0312923

Abstract: The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to ... ...

Abstract	The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid interface were used to model upper respiratory infection and compared to cell lines derived from human lung epithelia. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses, including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation, and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN-stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper respiratory tract and least favorable in the lower respiratory cell line, and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals. Importance: Comparative analysis of infections by SARS-CoV-2 ancestral virus and variants of concern, including Alpha, Beta, Delta, and Omicron, indicated that variants were selected for efficiency in replication. In infections of patient-derived primary nasal cultures grown at air-liquid interface to model upper respiratory infection, Omicron reached the highest titers at early time points, a finding that was confirmed by parallel population sampling studies. While all infections overcame dsRNA-mediated host responses, infections with Omicron induced the strongest interferon and interferon-stimulated gene response. In both primary nasal cultures and lower respiratory cell line, infections by Delta were most damaging to the cells as indicated by syncytia formation, loss of cell barrier integrity, and nasal ciliary function.
Mesh-Begriff(e)	Humans ; COVID-19 ; SARS-CoV-2/genetics ; Cell Line ; Interferons
Chemische Substanzen	Interferons (9008-11-1)
Sprache	Englisch
Erscheinungsdatum	2024-03-13
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.03129-23
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Tracking gut microbiome and bloodstream infection in critically ill adults.

Gu, Christopher H / Khatib, Layla A / Fitzgerald, Ayannah S / Graham-Wooten, Jevon / Ittner, Caroline A / Sherrill-Mix, Scott / Chuang, YuChung / Glaser, Laurel J / Meyer, Nuala J / Bushman, Frederic D / Collman, Ronald G

PloS one

2023 Band 18, Heft 10, Seite(n) e0289923

Abstract: Background: The gut microbiome is believed to contribute to bloodstream infection (BSI) via translocation of dominant gut bacteria in vulnerable patient populations. However, conclusively linking gut and blood organisms requires stringent approaches to ... ...

Abstract	Background: The gut microbiome is believed to contribute to bloodstream infection (BSI) via translocation of dominant gut bacteria in vulnerable patient populations. However, conclusively linking gut and blood organisms requires stringent approaches to establish strain-level identity. Methods: We enrolled a convenience cohort of critically ill patients and investigated 86 bloodstream infection episodes that occurred in 57 patients. Shotgun metagenomic sequencing was used to define constituents of their gut microbiomes, and whole genome sequencing and assembly was done on 23 unique bloodstream isolates that were available from 21 patients. Whole genome sequences were downloaded from public databases and used to establish sequence-identity distribution and define thresholds for unrelated genomes of BSI species. Gut microbiome reads were then aligned to whole genome sequences of the cognate bloodstream isolate and unrelated database isolates to assess identity. Results: Gut microbiome constituents matching the bloodstream infection species were present in half of BSI episodes, and represented >30% relative abundance of gut sequences in 10% of episodes. Among the 23 unique bloodstream organisms that were available for whole genome sequencing, 14 were present in gut at the species level. Sequence alignment applying defined thresholds for identity revealed that 6 met criteria for identical strains in blood and gut, but 8 did not. Sequence identity between BSI isolates and gut microbiome reads was more likely when the species was present at higher relative abundance in gut. Conclusion: In assessing potential gut source for BSI, stringent sequence-based approaches are essential to determine if organisms responsible for BSI are identical to those in gut: of 14 evaluable patients in which the same species was present in both sites, they were identical in 6/14, but were non-identical in 8/14 and thus inconsistent with gut source. This report demonstrates application of sequencing as a key tool to investigate infection tracking within patients.
Mesh-Begriff(e)	Humans ; Adult ; Gastrointestinal Microbiome/genetics ; Bacteremia/microbiology ; Critical Illness ; Sepsis ; Bacteria/genetics
Sprache	Englisch
Erscheinungsdatum	2023-10-10
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0289923
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The HIV-1 Capsid-Targeted Inhibitor GSK878 Alters Selection of Target Sites for HIV DNA Integration.

Marquis, Kaitlin A / Everett, John / Cantu, Adrian / McFarland, Alexander / Sherrill-Mix, Scott / Krystal, Mark / Parcella, Kyle / Gillis, Eric / Fridell, Robert A / Bushman, Frederic D

AIDS research and human retroviruses

2023 Band 40, Heft 2, Seite(n) 114–126

Abstract: Decades of effort have yielded highly effective antiviral agents to treat HIV, but viral strains have evolved resistance to each inhibitor type, focusing attention on the importance of developing new inhibitor classes. A particularly promising new target ...

Abstract	Decades of effort have yielded highly effective antiviral agents to treat HIV, but viral strains have evolved resistance to each inhibitor type, focusing attention on the importance of developing new inhibitor classes. A particularly promising new target is the HIV capsid, the function of which can be disrupted by highly potent inhibitors that persist long term in treated subjects. Studies with such inhibitors have contributed to an evolving picture of the role of capsid itself-the inhibitors, like certain capsid protein (CA) amino acid substitutions, can disrupt intracellular trafficking to alter the selection of target sites for HIV DNA integration in cellular chromosomes. In this study, we compare effects on HIV integration targeting for two potent inhibitors-a new molecule targeting CA, GSK878, and the previously studied lenacapavir (LEN, formerly known as GS-6207). We find that both inhibitors reduce integration in active transcription units and near epigenetic marks associated with active transcription. A careful study of integration near repeated sequences indicated frequencies were also altered for integration within multiple repeat classes. One notable finding was increased integration in centromeric satellite repeats in the presence of LEN and GSK878, which is of interest because proviruses integrated in centromeric repeats have been associated with transcriptional repression, inducibility, and latency. These data add to the picture that CA protein remains associated with preintegration complexes through the point in infection during which target sites for integration are selected, and specify new aspects of the consequences of disrupting this mechanism.
Mesh-Begriff(e)	Humans ; Capsid/metabolism ; Capsid Proteins/genetics ; Capsid Proteins/metabolism ; HIV-1 ; HIV Infections/genetics ; DNA, Viral/genetics ; Virus Integration
Chemische Substanzen	Capsid Proteins ; DNA, Viral
Sprache	Englisch
Erscheinungsdatum	2023-06-07
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/AID.2022.0161
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.

bioRxiv : the preprint server for biology

2023

Abstract: The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to ... ...

Abstract	The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell-barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper-respiratory system and least-favorable in the lower-respiratory cell line; and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals.
Sprache	Englisch
Erscheinungsdatum	2023-12-21
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.08.24.553565
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Gene activity in primary T cells infected with HIV89.6: intron retention and induction of genomic repeats.

Sherrill-Mix, Scott / Ocwieja, Karen E / Bushman, Frederic D

Retrovirology

2015 Band 12, Seite(n) 79

Abstract: Background: HIV infection has been reported to alter cellular gene activity, but published studies have commonly assayed transformed cell lines and lab-adapted HIV strains, yielding inconsistent results. Here we carried out a deep RNA-Seq analysis of ... ...

Abstract	Background: HIV infection has been reported to alter cellular gene activity, but published studies have commonly assayed transformed cell lines and lab-adapted HIV strains, yielding inconsistent results. Here we carried out a deep RNA-Seq analysis of primary human T cells infected with the low passage HIV isolate HIV89.6. Results: Seventeen percent of cellular genes showed altered activity 48 h after infection. In a meta-analysis including four other studies, our data differed from studies of HIV infection in cell lines but showed more parallels with infections of primary cells. We found a global trend toward retention of introns after infection, suggestive of a novel cellular response to infection. HIV89.6 infection was also associated with activation of several human endogenous retroviruses (HERVs) and retrotransposons, of interest as possible novel antigens that could serve as vaccine targets. The most highly activated group of HERVs was a subset of the ERV-9. Analysis showed that activation was associated with a particular variant of ERV-9 long terminal repeats that contains an indel near the U3-R border. These data also allowed quantification of >70 splice forms of the HIV89.6 RNA and specified the main types of chimeric HIV89.6-host RNAs. Comparison to over 100,000 integration site sequences from the same infected cell populations allowed quantification of authentic versus artifactual chimeric reads, showing that 5' read-in, splicing out of HIV89.6 from the D4 donor and 3' read-through were the most common HIV89.6-host cell chimeric RNA forms. Conclusions: Analysis of RNA abundance after infection of primary T cells with the low passage HIV89.6 isolate disclosed multiple novel features of HIV-host interactions, notably intron retention and induction of transcription of retrotransposons and endogenous retroviruses.
Mesh-Begriff(e)	Cell Line ; Cells, Cultured ; Endogenous Retroviruses/physiology ; HIV-1/physiology ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Humans ; Introns ; Retroelements ; T-Lymphocytes/metabolism ; T-Lymphocytes/virology ; Transcriptional Activation ; Virus Activation
Chemische Substanzen	Retroelements
Sprache	Englisch
Erscheinungsdatum	2015-09-17
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1742-4690
ISSN (online)	1742-4690
DOI	10.1186/s12977-015-0205-1
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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