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  1. Article ; Online: Interplay between RNA Viruses and Promyelocytic Leukemia Nuclear Bodies

    Sabari Nath Neerukonda

    Veterinary Sciences, Vol 8, Iss 57, p

    2021  Volume 57

    Abstract: Promyelocytic leukemia nuclear bodies (PML NBs) are nuclear membrane-less sub structures that play a critical role in diverse cellular pathways including cell proliferation, DNA damage, apoptosis, transcriptional regulation, stem cell renewal, ... ...

    Abstract Promyelocytic leukemia nuclear bodies (PML NBs) are nuclear membrane-less sub structures that play a critical role in diverse cellular pathways including cell proliferation, DNA damage, apoptosis, transcriptional regulation, stem cell renewal, alternative lengthening of telomeres, chromatin organization, epigenetic regulation, protein turnover, autophagy, intrinsic and innate antiviral immunity. While intrinsic and innate immune functions of PML NBs or PML NB core proteins are well defined in the context of nuclear replicating DNA viruses, several studies also confirm their substantial roles in the context of RNA viruses. In the present review, antiviral activities of PML NBs or its core proteins on diverse RNA viruses that replicate in cytoplasm or the nucleus were discussed. In addition, viral counter mechanisms that reorganize PML NBs, and specifically how viruses usurp PML NB functions in order to create a cellular environment favorable for replication and pathogenesis, are also discussed.
    Keywords promyelocytic leukemia ; nuclear bodies ; RNA virus ; small ubiquitin modifier ; innate immunity ; proteasome ; Veterinary medicine ; SF600-1100
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Avian Pattern Recognition Receptor Sensing and Signaling

    Sabari Nath Neerukonda / Upendra Katneni

    Veterinary Sciences, Vol 7, Iss 1, p

    2020  Volume 14

    Abstract: Pattern recognition receptors (PRRs) are a class of immune sensors that play a critical role in detecting and responding to several conserved patterns of microorganisms. As such, they play a major role in the maintenance of immune homeostasis and anti- ... ...

    Abstract Pattern recognition receptors (PRRs) are a class of immune sensors that play a critical role in detecting and responding to several conserved patterns of microorganisms. As such, they play a major role in the maintenance of immune homeostasis and anti-microbial defense. Fundamental knowledge pertaining to the discovery of PRR functions and their ligands continue to advance the understanding of immune system and disease resistance, which led to the rational design and/or application of various PRR ligands as vaccine adjuvants. In addition, the conserved nature of many PRRs throughout the animal kingdom has enabled the utilization of the comparative genomics approach in PRR identification and the study of evolution, structural features, and functions in many animal species including avian. In the present review, we focused on PRR sensing and signaling functions in the avian species, domestic chicken, mallard, and domestic goose. In addition to summarizing recent advances in the understanding of avian PRR functions, the present review utilized a comparative biology approach to identify additional PRRs, whose functions have been well studied in mammalians but await functional characterization in avian.
    Keywords innate immunity ; pattern recognition receptors ; pathogen sensing ; signaling ; Veterinary medicine ; SF600-1100
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Book ; Online: A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions

    Sabari Nath Neerukonda / Upendra Katneni

    Pathogens ; Volume 9 ; Issue 6

    2020  

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials.
    Keywords SARS-CoV-2 ; COVID-19 ; animal models ; antivirals ; covid19
    Subject code 610
    Language English
    Publishing date 2020-05-29
    Publisher Multidisciplinary Digital Publishing Institute
    Publishing country ch
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions

    Sabari Nath Neerukonda / Upendra Katneni

    Pathogens, Vol 9, Iss 426, p

    2020  Volume 426

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials.
    Keywords SARS-CoV-2 ; COVID-19 ; animal models ; antivirals ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Neutralizing Antibodies Targeting the Conserved Stem Region of Influenza Hemagglutinin

    Sabari Nath Neerukonda / Russell Vassell / Carol D. Weiss

    Vaccines, Vol 8, Iss 382, p

    2020  Volume 382

    Abstract: Influenza continues to be a public health threat despite the availability of annual vaccines. While vaccines are generally effective at inducing strain-specific immunity, they are sub-optimal or ineffective when drifted or novel pandemic strains arise ... ...

    Abstract Influenza continues to be a public health threat despite the availability of annual vaccines. While vaccines are generally effective at inducing strain-specific immunity, they are sub-optimal or ineffective when drifted or novel pandemic strains arise due to sequence changes in the major surface glycoprotein hemagglutinin (HA). The discovery of a large number of antibodies targeting the highly conserved stem region of HAs that are capable of potently neutralizing a broad range of virus strains and subtypes suggests new ways to protect against influenza. The structural characterization of HA stem epitopes and broadly neutralizing antibody paratopes has enabled the design of novel proteins, mini-proteins, and peptides targeting the HA stem, thus providing a foundation for the design of new vaccines. In this narrative, we comprehensively review the current knowledge about stem-directed broadly neutralizing antibodies and the structural features contributing to virus neutralization.
    Keywords influenza ; hemagglutinin ; broadly neutralizing antibodies ; universal influenza vaccines ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy

    Kiruphagaran Thangaraju / Sabari Nath Neerukonda / Upendra Katneni / Paul W. Buehler

    International Journal of Molecular Sciences, Vol 22, Iss 153, p

    2021  Volume 153

    Abstract: Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-derived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease ... ...

    Abstract Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-derived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease conditions, and in response to environmental stressors. RBCEVs are enriched in various bioactive molecules that facilitate cell to cell communication and can act as markers of disease. RBCEVs contribute towards physiological adaptive responses to hypoxia as well as pathophysiological progression of diabetes and genetic non-malignant hematologic disease. Moreover, a considerable number of studies focus on the role of EVs from stored RBCs and have evaluated post transfusion consequences associated with their exposure. Interestingly, RBCEVs are important contributors toward coagulopathy in hematological disorders, thus representing a unique evolving area of study that can provide insights into molecular mechanisms that contribute toward dysregulated hemostasis associated with several disease conditions. Relevant work to this point provides a foundation on which to build further studies focused on unraveling the potential roles of RBCEVs in health and disease. In this review, we provide an analysis and summary of RBCEVs biogenesis, composition, and their biological function with a special emphasis on RBCEV pathophysiological contribution to coagulopathy. Further, we consider potential therapeutic applications of RBCEVs.
    Keywords red blood cells ; extracellular vesicles ; exosomes ; microvesicles ; microparticles ; cell-to-cell communication ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Effects of N-glycan modifications on spike expression, virus infectivity, and neutralization sensitivity in ancestral compared to Omicron SARS-CoV-2 variants.

    Sabrina Lusvarghi / Charles B Stauft / Russell Vassell / Brittany Williams / Haseebullah Baha / Wei Wang / Sabari Nath Neerukonda / Tony Wang / Carol D Weiss

    PLoS Pathogens, Vol 19, Iss 11, p e

    2023  Volume 1011788

    Abstract: The SARS-CoV-2 spike glycoprotein has 22 potential N-linked glycosylation sites per monomer that are highly conserved among diverse variants, but how individual glycans affect virus entry and neutralization of Omicron variants has not been extensively ... ...

    Abstract The SARS-CoV-2 spike glycoprotein has 22 potential N-linked glycosylation sites per monomer that are highly conserved among diverse variants, but how individual glycans affect virus entry and neutralization of Omicron variants has not been extensively characterized. Here we compared the effects of specific glycan deletions or modifications in the Omicron BA.1 and D614G spikes on spike expression, processing, and incorporation into pseudoviruses, as well as on virus infectivity and neutralization by therapeutic antibodies. We found that loss of potential glycans at spike residues N717 and N801 each conferred a loss of pseudovirus infectivity for Omicron but not for D614G or Delta variants. This decrease in infectivity correlated with decreased spike processing and incorporation into Omicron pseudoviruses. Oligomannose-enriched Omicron pseudoviruses generated in GnTI- cells or in the presence of kifunensine were non-infectious, whereas D614G or Delta pseudoviruses generated under similar conditions remained infectious. Similarly, growth of live (authentic) SARS-CoV-2 in the presence of kifunensine resulted in a greater reduction of titers for the BA.1.1 variant than Delta or D614G variants relative to their respective, untreated controls. Finally, we found that loss of some N-glycans, including N343 and N234, increased the maximum percent neutralization by the class 3 S309 monoclonal antibody against D614G but not BA.1 variants, while these glycan deletions altered the neutralization potency of the class 1 COV2-2196 and Etesevimab monoclonal antibodies without affecting maximum percent neutralization. The maximum neutralization by some antibodies also varied with the glycan composition, with oligomannose-enriched pseudoviruses conferring the highest percent neutralization. These results highlight differences in the interactions between glycans and residues among SARS-CoV-2 variants that can affect spike expression, virus infectivity, and susceptibility of variants to antibody neutralization.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Establishment of a well-characterized SARS-CoV-2 lentiviral pseudovirus neutralization assay using 293T cells with stable expression of ACE2 and TMPRSS2.

    Sabari Nath Neerukonda / Russell Vassell / Rachel Herrup / Shufeng Liu / Tony Wang / Kazuyo Takeda / Ye Yang / Tsai-Lien Lin / Wei Wang / Carol D Weiss

    PLoS ONE, Vol 16, Iss 3, p e

    2021  Volume 0248348

    Abstract: Pseudoviruses are useful surrogates for highly pathogenic viruses because of their safety, genetic stability, and scalability for screening assays. Many different pseudovirus platforms exist, each with different advantages and limitations. Here we report ...

    Abstract Pseudoviruses are useful surrogates for highly pathogenic viruses because of their safety, genetic stability, and scalability for screening assays. Many different pseudovirus platforms exist, each with different advantages and limitations. Here we report our efforts to optimize and characterize an HIV-based lentiviral pseudovirus assay for screening neutralizing antibodies for SARS-CoV-2 using a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We assessed different target cells, established conditions that generate readouts over at least a two-log range, and confirmed consistent neutralization titers over a range of pseudovirus input. Using reference sera and plasma panels, we evaluated assay precision and showed that our neutralization titers correlate well with results reported in other assays. Overall, our lentiviral assay is relatively simple, scalable, and suitable for a variety of SARS-CoV-2 entry and neutralization screening assays.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: A comparison of exosome purification methods using serum of Marek's disease virus (MDV)-vaccinated and -tumor-bearing chickens

    Sabari Nath Neerukonda / Nicholas A. Egan / Joseph Patria / Imane Assakhi / Phaedra Tavlarides-Hontz / Shannon Modla / Eric R. Muñoz / Matthew B. Hudson / Mark S. Parcells

    Heliyon, Vol 6, Iss 12, Pp e05669- (2020)

    2020  

    Abstract: Marek's disease (MD) is an alphaherpesvirus (Marek's disease virus, MDV)-induced pathology of chickens associated with paralysis, immunosuppression, neurological signs, and T-cell lymphomas. MD is controlled in poultry production via live attenuated ... ...

    Abstract Marek's disease (MD) is an alphaherpesvirus (Marek's disease virus, MDV)-induced pathology of chickens associated with paralysis, immunosuppression, neurological signs, and T-cell lymphomas. MD is controlled in poultry production via live attenuated vaccines. The purpose of the current study was to compare methods for precipitating exosomes from vaccinated and protected chicken sera (VEX) and tumor-bearing chicken sera (TEX) for biomarker analysis of vaccine-induced protection and MD lymphomas respectively. A standard polyethylene glycol (PEG, 8%) method was compared to a commercial reagent (total exosome isolation reagent, TEI) for exosome yield and RNA content. Although exosomes purified by PEG or TEI were comparable in size and morphology, TEI-reagent yielded 3-4-fold greater concentration. Relative expression of 8 out of 10 G. gallus- and MDV1-encoded miRNAs examined displayed significant difference depending upon the precipitation method used. Standard PEG yields comparable, albeit lower amounts of exosomes than the TEI-reagent and a distinctive miRNA composition.
    Keywords Immunology ; Virology ; Animal science ; Transcriptomics ; Veterinary medicine ; Hematological system ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
    Subject code 630
    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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