UNC-Chapel Hill Coronavirus Research

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A collection of articles and student papers related to coronaviruses that have been authored by researchers at the University of North Carolina at Chapel Hill.

Works (1052)

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971. Effects of Human Anti-Spike Protein Receptor Binding Domain Antibodies on Severe Acute Respiratory Syndrome Coronavirus Neutralization Escape and Fitness

Title Tesim:
Effects of Human Anti-Spike Protein Receptor Binding Domain Antibodies on Severe Acute Respiratory Syndrome Coronavirus Neutralization Escape and Fitness
Creator:
Robert C. Liddington, Quan Karen Zhu, Meagan Deming, Barry Rockx, Jianhua Sui, Wayne A. Marascoa, and Ralph S. Baric
Date of publication:
2014
Abstract Tesim:
The receptor binding domain (RBD) of the spike (S) glycoprotein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major target of protective immunity in vivo. Although a large number of neutralizing antibodies (nAbs) have been developed, it remains unclear if a single RBD-targeting nAb or two in combination can prevent neutralization escape and, if not, attenuate viral virulence in vivo. In this study, we used a large panel of human nAbs against an epitope that overlaps the interface between the RBD and its receptor, angiotensin-converting enzyme 2 (ACE2), to assess their cross-neutralization activities against a panel of human and zoonotic SARS-CoVs and neutralization escape mutants. We also investigated the neutralization escape profiles of these nAbs and evaluated their effects on receptor binding and virus fitness in vitro and in mice. We found that some nAbs had great potency and breadth in neutralizing multiple viral strains, including neutralization escape viruses derived from other nAbs; however, no single nAb or combination of two blocked neutralization escape. Interestingly, in mice the neutralization escape mutant viruses showed either attenuation (Urbani background) or increased virulence (GD03 background) consistent with the different binding affinities between their RBDs and the mouse ACE2. We conclude that using either single nAbs or dual nAb combinations to target a SARS-CoV RBD epitope that shows plasticity may have limitations for preventing neutralization escape during in vivo immunotherapy. However, RBD-directed nAbs may be useful for providing broad neutralization and prevention of escape variants when combined with other nAbs that target a second conserved epitope with less plasticity and more structural constraint.
Resource type:
Article
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/3qjm-qq07
ISSN:
1070-6321, 1098-5514, and 0022-538X
Journal Issue:
23
Journal Title:
Journal of Virology
Journal Volume:
88
Keyword:
Severe Acute Respiratory Syndrome, Virulence, In Vitro Techniques, Immunity, Virus Attachment, Carrier Proteins, Homo sapiens, Coronavirus Infections, Receptors, Angiotensin, Mortality, ACE2, Infection, Antibodies, Neutralizing, Ace2 , Immunotherapy, Glycoproteins, Epitopes, Enzymes, Mus musculus, and Antibodies
Language Label:
English
ORCID:
Other Affiliation:
Infectious and Inflammatory Disease Center, Stanford-Burnham Medical Research Institute, La Jolla, California, USA, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute; Department of Medicine, Harvard Medical School, Boston Massachusetts, USA, and Departments of Epidemiology and Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA
Page End:
13780
Page Start:
13769
Person:
Robert C. Liddington, Quan Karen Zhu, Meagan Deming, Barry Rockx, Jianhua Sui, Wayne A. Marascoa, and Ralph S. Baric
Publisher:
American Society for Microbiology
Rights Statement Label:
In Copyright
Source:
pr76f789v

972. Coronavirus Replicase-Reporter Fusions Provide Quantitative Analysis of Replication and Replication Complex Formation

Title Tesim:
Coronavirus Replicase-Reporter Fusions Provide Quantitative Analysis of Replication and Replication Complex Formation
Creator:
Xiaotao Lu, Megan Culler Freeman, Christopher T. Peek, Rachel L. Graham, and Mark R. Denison
Date of publication:
2014
Abstract Tesim:
The replication of coronaviruses occurs in association with multiple virus-induced membrane structures that evolve during the course of infection; however, the dynamics of this process remain poorly understood. Previous studies of coronavirus replication complex organization and protein interactions have utilized protein overexpression studies and immunofluorescence of fixed cells. Additionally, live-imaging studies of coronavirus replicase proteins have used fluorescent reporter molecules fused to replicase proteins, but expressed from nonnative locations, mostly late-transcribed subgenomic mRNAs, in the presence or absence of the native protein. Thus, the timing and targeting of native replicase proteins expressed in real time from native locations in the genome remain unknown. In this study, we tested whether reporter molecules could be expressed from the replicase polyprotein of murine hepatitis virus as fusions with nonstructural protein 2 or 3 and whether such reporters could define the targeting and activity of replicase proteins during infection. We demonstrate that the fusion of green fluorescent protein and firefly luciferase with either nonstructural protein 2 or 3 is tolerated and that these reporter-replicase fusions can be used to quantitate replication complex formation and virus replication. The results show that the replicase gene has flexibility to accommodate a foreign gene addition and can be used directly to study replicase complex formation and evolution during infection as well as to provide highly sensitive and specific markers for protein translation and genome replication.
Resource type:
Article
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/gwrw-ms81
ISSN:
0022-538X, 1098-5514, and 1070-6321
Journal Issue:
10
Journal Title:
Journal of Virology
Journal Volume:
88
Keyword:
Proteins, Cells, Coronavirus Infections, Ambp, Mus musculus, RNA, Fluorescent Antibody Technique, Polyproteins, Membranes, Genome, Green Fluorescent Proteins, Genes, Hepatitis, Luciferases, Firefly, Severe Acute Respiratory Syndrome, Virus Replication, Infection, and Protein Biosynthesis
Language Label:
English
ORCID:
Other Affiliation:
Departments of Pediatrics and Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Departments of Pathology, Microbiology, and Immunology, and Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA, and Departments of Pediatrics and Pathology, Microbiology, and Immunology, and Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Page End:
5327
Page Start:
5319
Person:
Xiaotao Lu, Megan Culler Freeman, Christopher T. Peek, Rachel L. Graham, and Mark R. Denison
Publisher:
American Society for Microbiology
Rights Statement Label:
In Copyright
Source:
0z7092114

973. Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice

Title Tesim:
Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice
Creator:
Cameron, Mark, Donaldson, Eric, Rockx, Barry, Pickles, Raymond, Harkema, Jack, Sims, Amy, Sheahan, Timothy, Kelvin, David, Heise, Mark, and Baric, Ralph
Date of publication:
2007
Abstract Tesim:
The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.
Resource type:
Article
Admin Note:
deposited as part of the 1Science upload
Affiliation Label Tesim:
Department of Microbiology and Immunology and Department of Epidemiology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/1tjz-xj23
Identifier:
https://dx.doi.org/10.1128/JVI.00505-07
ISSN:
0022-538X
Journal Issue:
14
Journal Title:
Journal of Virology
Journal Volume:
81
Keyword:
Human, Isolate, Rodentia, Acute, Animal, Mouse, Death, Coronavirus, Virology, Virus, Mammalia, and Vertebrata
Language Label:
English
ORCID:
Other Affiliation:
University of Toronto, , and Michigan State University
Page End:
7423
Page Start:
7410
Person:
Cameron, Mark, Donaldson, Eric, Rockx, Barry, Pickles, Raymond, Harkema, Jack, Sims, Amy, Sheahan, Timothy, Kelvin, David, Heise, Mark, and Baric, Ralph
Rights Statement Label:
In Copyright
Source:
x633f5302

974. Severe Acute Respiratory Syndrome Coronavirus ORF6 Antagonizes STAT1 Function by Sequestering Nuclear Import Factors on the Rough Endoplasmic Reticulum/Golgi Membrane

Title Tesim:
Severe Acute Respiratory Syndrome Coronavirus ORF6 Antagonizes STAT1 Function by Sequestering Nuclear Import Factors on the Rough Endoplasmic Reticulum/Golgi Membrane
Creator:
Frieman, Matthew, Kopecky-Bromberg, Sarah A., Yount, Boyd, Palese, Peter, Heise, Mark, and Baric, Ralph S.
Date of publication:
2007
Abstract Tesim:
The host innate immune response is an important deterrent of severe viral infection in humans and animals. Nuclear import factors function as key gatekeepers that regulate the transport of innate immune regulatory cargo to the nucleus of cells to activate the antiviral response. Using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model, we demonstrate that SARS-COV ORF6 protein is localized to the endoplasmic reticulum (ER)/Golgi membrane in infected cells, where it binds to and disrupts nuclear import complex formation by tethering karyopherin alpha 2 and karyopherin beta 1 to the membrane. Retention of import factors at the ER/Golgi membrane leads to a loss of STAT1 transport into the nucleus in response to interferon signaling, thus blocking the expression of STAT1-activated genes that establish an antiviral state. We mapped the region of ORF6, which binds karyopherin alpha 2, to the C terminus of ORF6 and show that mutations in the C terminus no longer bind karyopherin alpha 2 or block the nuclear import of STAT1. We also show that N-terminal deletions of karyopherin alpha 2 that no longer bind to karyopherin beta 1 still retain ORF6 binding activity but no longer block STAT1 nuclear import. Recombinant SARS-CoV lacking ORF6 did not tether karyopherin alpha 2 to the ER/Golgi membrane and allowed the import of the STAT1 complex into the nucleus. We discuss the likely implications of these data on SARS-CoV replication and pathogenesis.
Resource type:
Article
Admin Note:
deposited as part of the 1Science upload
Affiliation Label Tesim:
Department of Epidemiology and Department of Microbiology and Immunology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/s985-yf81
Identifier:
https://dx.doi.org/10.1128/JVI.01012-07
ISSN:
0022-538X
Journal Issue:
18
Journal Title:
Journal of Virology
Journal Volume:
81
Keyword:
Virology, Virus, Endoplasmic reticulum, Coronavirus, Acute, and Golgi apparatus
Language Label:
English
ORCID:
Other Affiliation:
and Mount Sinai School of Medicine
Page End:
9824
Page Start:
9812
Person:
Frieman, Matthew, Kopecky-Bromberg, Sarah A., Yount, Boyd, Palese, Peter, Heise, Mark, and Baric, Ralph S.
Rights Statement Label:
In Copyright
Source:
j098zg86w

975. Attenuation and Restoration of Severe Acute Respiratory Syndrome Coronavirus Mutant Lacking 2'-O-Methyltransferase Activity

Title Tesim:
Attenuation and Restoration of Severe Acute Respiratory Syndrome Coronavirus Mutant Lacking 2'-O-Methyltransferase Activity
Creator:
Michael G. Katze, Sudhakar Agnihothram, Boyd L. Yount, Jr., Lisa E. Gralinski, Ralph S. Baric, Trevor Scobey, Laurence Josset, and Vineet D. Menachery
Date of publication:
2014
Abstract Tesim:
The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and, more recently, Middle Eastern respiratory syndrome CoV (MERS-CoV) underscores the importance of understanding critical aspects of CoV infection and pathogenesis. Despite significant insights into CoV cross-species transmission, replication, and virus-host interactions, successful therapeutic options for CoVs do not yet exist. Recent identification of SARS-CoV NSP16 as a viral 2′-O-methyltransferase (2′-O-MTase) led to the possibility of utilizing this pathway to both attenuate SARS-CoV infection and develop novel therapeutic treatment options. Mutations were introduced into SARS-CoV NSP16 within the conserved KDKE motif and effectively attenuated the resulting SARS-CoV mutant viruses both in vitro and in vivo. While viruses lacking 2′-O-MTase activity had enhanced sensitivity to type I interferon (IFN), they were not completely restored in their absence in vivo. However, the absence of either MDA5 or IFIT1, IFN-responsive genes that recognize unmethylated 2′-O RNA, resulted in restored replication and virulence of the dNSP16 mutant virus. Finally, using the mutant as a live-attenuated vaccine showed significant promise for possible therapeutic development against SARS-CoV. Together, the data underscore the necessity of 2′-O-MTase activity for SARS-CoV pathogenesis and identify host immune pathways that mediate this attenuation. In addition, we describe novel treatment avenues that exploit this pathway and could potentially be used against a diverse range of viral pathogens that utilize 2′-O-MTase activity to subvert the immune system.
Resource type:
Article
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/8qve-1v06
ISSN:
0022-538X, 1070-6321, and 1098-5514
Journal Issue:
8
Journal Title:
Journal of Virology
Journal Volume:
88
Keyword:
Virus Replication, Amino Acid Motifs, Animals, Virulence, Mice, Interferon-Induced Helicase, IFIH1, Methyltransferases, Male, Ifit1 protein, mouse, Mice, Inbred C57BL, Humans, SARS Virus, Female, Mutation, Mice, Inbred BALB C, Viral Nonstructural Proteins, DEAD-box RNA Helicases, Nsp16 protein, SARS virus, Severe Acute Respiratory Syndrome, and Carrier Proteins
Language Label:
English
ORCID:
Other Affiliation:
Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA ; Washington National Primate Research Center, University of Washington, Seattle, Washington, USA, Departments of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA, Departments of Epidemiology and Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA, and Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA
Page End:
4264
Page Start:
4251
Person:
Michael G. Katze, Sudhakar Agnihothram, Boyd L. Yount, Jr., Lisa E. Gralinski, Ralph S. Baric, Trevor Scobey, Laurence Josset, and Vineet D. Menachery
Publisher:
American Society for Microbiology
Rights Statement Label:
In Copyright
Source:
7d278z878

976. Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists

Title Tesim:
Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists
Creator:
Martinez-Sobrido, Luis, Baric, Ralph, Frieman, Matthew, Kopecky-Bromberg, Sarah A., and Palese, Peter
Date of publication:
2007
Abstract Tesim:
The severe acute respiratory syndrome coronavirus (SARS-CoV) is highly pathogenic in humans, with a death rate near 10%. This high pathogenicity suggests that SARS-CoV has developed mechanisms to overcome the host innate immune response. It has now been determined that SARS-CoV open reading frame (ORF) 3b, ORF 6, and N proteins antagonize interferon, a key component of the innate immune response. All three proteins inhibit the expression of beta interferon (IFN-β), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-β, IRF-3. N protein dramatically inhibited expression from an NF-κB-responsive promoter. All three proteins were able to inhibit expression from an interferon-stimulated response element (ISRE) promoter after infection with Sendai virus, while only ORF 3b and ORF 6 proteins were able to inhibit expression from the ISRE promoter after treatment with interferon. This indicates that N protein inhibits only the synthesis of interferon, while ORF 3b and ORF 6 proteins inhibit both interferon synthesis and signaling. ORF 6 protein, but not ORF 3b or N protein, inhibited nuclear translocation but not phosphorylation of STAT1. Thus, it appears that these three interferon antagonists of SARS-CoV inhibit the interferon response by different mechanisms.
Resource type:
Article
Admin Note:
deposited as part of the 1Science batch
Affiliation Label Tesim:
University of North Carolina at Chapel Hill
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/z5e0-xe64
Identifier:
https://dx.doi.org/10.1128/JVI.01782-06
ISSN:
0022-538X
Journal Issue:
2
Journal Title:
Journal of Virology
Journal Volume:
81
Keyword:
Protein, Interferon, Coronavirus, Respiratory disease, Severe acute respiratory syndrome, Nucleocapsid, Open reading frame, Infection, Virus, Virology, Viral disease, and Lung disease
Language Label:
English
ORCID:
Other Affiliation:
Mount Sinai School of Medicine and
Page End:
557
Page Start:
548
Person:
Martinez-Sobrido, Luis, Baric, Ralph, Frieman, Matthew, Kopecky-Bromberg, Sarah A., and Palese, Peter
Rights Statement Label:
In Copyright
Source:
5h73q1315

977. Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain

Title Tesim:
Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain
Creator:
Baric, Ralph S., Frieman, Matthew, Wathelet, Marc G., and Orr, Melissa
Date of publication:
2007
Abstract Tesim:
The severe acute respiratory syndrome (SARS) epidemic was caused by the spread of a previously unrecognized infectious agent, the SARS-associated coronavirus (SARS-CoV). Here we show that SARS-CoV could inhibit both virus- and interferon (IFN)-dependent signaling, two key steps of the antiviral response. We mapped a strong inhibitory activity to SARS-CoV nonstructural protein 1 (nsp1) and show that expression of nsp1 significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nsp1 significantly inhibited IFN-dependent signaling by decreasing the phosphorylation levels of STAT1 while having little effect on those of STAT2, JAK1, and TYK2. We engineered an attenuated mutant of nsp1 in SARS-CoV through reverse genetics, and the resulting mutant virus was viable and replicated as efficiently as wild-type virus in cells with a defective IFN response. However, mutant virus replication was strongly attenuated in cells with an intact IFN response. Thus, nsp1 is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication.
Resource type:
Article
Admin Note:
deposited as part of the 1Science batch
Affiliation Label Tesim:
Department of Epidemiology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/cxm9-cx68
Identifier:
https://dx.doi.org/10.1128/JVI.00702-07
ISSN:
0022-538X
Journal Issue:
21
Journal Title:
Journal of Virology
Journal Volume:
81
Keyword:
Genes, Reporter, Vero Cells, RNA Replicase, Humans, Cell Line, Antiviral Agents, Promoter Regions, Genetic, SARS Virus, Viral Nonstructural Proteins, Models, Genetic, Animals, Cloning, Molecular, Interferons, Drug Resistance, Viral, Cercopithecus aethiops, and Interferon-beta
Language Label:
English
ORCID:
Other Affiliation:
and University of Cincinnati
Page End:
11633
Page Start:
11620
Person:
Baric, Ralph S., Frieman, Matthew, Wathelet, Marc G., and Orr, Melissa
Rights Statement Label:
In Copyright
Source:
ht24wq25m

978. A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-Like Proteases of Emerging Coronaviruses

Title Tesim:
A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-Like Proteases of Emerging Coronaviruses
Creator:
Anna M. Mielech, Michael W. Wilson, Andrew D. Mesecar, Sarah E. St. John, Daniel B. Nichols, Scott D. Larsen, Susan Baker, Xufang Deng, Sudhakar Agnihothram, Ralph S. Baric, and Deborah J. Lenschow
Date of publication:
2014
Abstract Tesim:
To combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. Here, we exploit a biosafety level 2 (BSL-2) chimeric Sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed against the papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV), a biosafety level 3 (BSL-3) pathogen. We engineered Sindbis virus to coexpress PLpro and a substrate, murine interferon-stimulated gene 15 (ISG15), and found that PLpro mediates removal of ISG15 (deISGylation) from cellular proteins. Mutation of the catalytic cysteine residue of PLpro or addition of a PLpro inhibitor blocked deISGylation in virus-infected cells. Thus, deISGylation is a marker of PLpro activity. Infection of alpha/beta interferon receptor knockout (IFNAR−/−) mice with these chimeric viruses revealed that PLpro deISGylation activity removed ISG15-mediated protection during viral infection. Importantly, administration of a PLpro inhibitor protected these mice from lethal infection, demonstrating the efficacy of a coronavirus protease inhibitor in a mouse model. However, this PLpro inhibitor was not sufficient to protect the mice from lethal infection with SARS-CoV MA15, suggesting that further optimization of the delivery and stability of PLpro inhibitors is needed. We extended the chimeric-virus platform to evaluate the papain-like protease/deISGylating activity of Middle East respiratory syndrome coronavirus (MERS-CoV) to provide a small-animal model to evaluate PLpro inhibitors of this recently emerged pathogen. This platform has the potential to be universally adaptable to other viral and cellular enzymes that have deISGylating activities.
Resource type:
Article
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/aftx-3z93
ISSN:
1098-5514, 1070-6321, and 0022-538X
Journal Issue:
20
Journal Title:
Journal of Virology
Journal Volume:
88
Keyword:
Infection, Protease Inhibitors, IFNAR1, Ifnar1, Mutation, Sindbis virus, Interferons, Proteins, Mus musculus, Cells, Enzymes, Cysteine, Coronavirus Infections, Severe Acute Respiratory Syndrome, Genes, Homo sapiens, Models, Animal, Antiviral Agents, Receptors, Interferon, and Papain
Language Label:
English
ORCID:
and https://orcid.org/0000-0001-6485-8143
Other Affiliation:
Department of Microbiology and Immunology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA, Vahlteich Medicinal Chemistry Core, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA, Departments of Biological Science and Chemistry, Purdue University, West Lafayette, Indiana, USA, Departments of Epidemiology and Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA, and Department of Internal Medicine and Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA
Page End:
11833
Page Start:
11825
Person:
Anna M. Mielech, Michael W. Wilson, Andrew D. Mesecar, Sarah E. St. John, Daniel B. Nichols, Scott D. Larsen, Susan Baker, Xufang Deng, Sudhakar Agnihothram, Ralph S. Baric, and Deborah J. Lenschow
Publisher:
American Society for Microbiology
Rights Statement Label:
In Copyright
Source:
qz20sz14z

979. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease

Title Tesim:
Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease
Creator:
DeDiego, Marta L., Baric, Ralph, Enjuanes, Luis, Deming, Damon, Sheahan, Tim, and Alvarez, Enrique
Date of publication:
2008
Abstract Tesim:
An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans.
Resource type:
Article
Admin Note:
deposited as part of the 1Science batch
Affiliation Label Tesim:
Department of Microbiology and Immunology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/g47p-ha27
Identifier:
https://dx.doi.org/10.1016/j.virusres.2007.01.021
ISSN:
0168-1702
Journal Issue:
1
Journal Title:
Virus Research
Journal Volume:
133
Keyword:
Cercopithecus aethiops, Cell Line, SARS Virus, Vaccines, DNA, Severe Acute Respiratory Syndrome, Mice, Genome, Viral, Humans, Viral Vaccines, Caco-2 Cells, Animals, Antigens, Viral, Vero Cells, and Cricetinae
Language Label:
English
ORCID:
Other Affiliation:
Centro Nacional de Biotecnologia and
Page End:
62
Page Start:
45
Person:
DeDiego, Marta L., Baric, Ralph, Enjuanes, Luis, Deming, Damon, Sheahan, Tim, and Alvarez, Enrique
Rights Statement Label:
In Copyright
Source:
9593v105w

980. SARS coronavirus replicase proteins in pathogenesis

Title Tesim:
SARS coronavirus replicase proteins in pathogenesis
Creator:
Graham, Rachel L., Sims, Amy C., Denison, Mark R., Eckerle, Lance D., and Sparks, Jennifer S.
Date of publication:
2008
Abstract Tesim:
Much progress has been made in understanding the role of structural and accessory proteins in the pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) infections. The SARS epidemic also brought new attention to the proteins translated from ORF1a and ORF1b of the input genome RNA, also known as the replicase/transcriptase gene. Evidence for change within the ORF1ab coding sequence during the SARS epidemic, as well as evidence from studies with other coronaviruses, indicates that it is likely that the ORF1ab proteins play roles in virus pathogenesis distinct from or in addition to functions directly involved in viral replication. Recent reverse genetic studies have confirmed that proteins of ORF1ab may be involved in cellular signaling and modification of cellular gene expression, as well as virulence by mechanisms yet to be determined. Thus, the evolution of the ORF1ab proteins may be determined as much by issues of host range and virulence as they are by specific requirements for intracellular replication.
Resource type:
Article
Admin Note:
deposited as part of 1Science batch
Affiliation Label Tesim:
Department of Epidemiology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/b3r8-eb91
Identifier:
https://dx.doi.org/10.1016/j.virusres.2007.02.017
ISSN:
0168-1702
Journal Issue:
1
Journal Title:
Virus Research
Journal Volume:
133
Keyword:
Cercopithecus aethiops, Viral Nonstructural Proteins, Open Reading Frames, Virulence, RNA Replicase, Animals, SARS Virus, Humans, Vero Cells, and Severe Acute Respiratory Syndrome
Language Label:
English
ORCID:
Other Affiliation:
Vanderbilt University Medical Center and
Page End:
100
Page Start:
88
Person:
Graham, Rachel L., Sims, Amy C., Denison, Mark R., Eckerle, Lance D., and Sparks, Jennifer S.
Rights Statement Label:
In Copyright
Source:
00000444w