LIVIVO - Search results -

Search results

Result 1 - 10 of total 15

Search options

Article ; Online: Temporal development and neutralising potential of antibodies against SARS-CoV-2 in hospitalised COVID-19 patients: An observational cohort study.

Murrell, Isa / Forde, Donall / Zelek, Wioleta / Tyson, Linda / Chichester, Lisa / Palmer, Nicki / Jones, Rachel / Morgan, B Paul / Moore, Catherine

PloS one

2021 Volume 16, Issue 1, Page(s) e0245382

Abstract: Antibody responses are important in the control of viral respiratory infection in the human host. What is not clear for SARS-CoV-2 is how rapidly this response occurs, or when antibodies with protective capability evolve. Hence, defining the events of ... ...

Abstract	Antibody responses are important in the control of viral respiratory infection in the human host. What is not clear for SARS-CoV-2 is how rapidly this response occurs, or when antibodies with protective capability evolve. Hence, defining the events of SARS-CoV-2 seroconversion and the time frame for the development of antibodies with protective potential may help to explain the different clinical presentations of COVID-19. Furthermore, accurate descriptions of seroconversion are needed to inform the best use of serological assays for diagnostic testing and serosurveillance studies. Here, we describe the humoral responses in a cohort of hospitalised COVID-19 patients (n = 19) shortly following the onset of symptoms. Commercial and 'in-house' serological assays were used to measure IgG antibodies against different SARS-CoV-2 structural antigens-Spike (S) S1 sub-unit and Nucleocapsid protein (NP)-and to assess the potential for virus neutralisation mediated specifically by inhibition of binding between the viral attachment protein (S protein) and cognate receptor (ACE-2). Antibody response kinetics varied amongst the cohort, with patients seroconverting within 1 week, between 1-2 weeks, or after 2 weeks, following symptom onset. Anti-NP IgG responses were generally detected earlier, but reached maximum levels slower, than anti-S1 IgG responses. The earliest IgG antibodies produced by all patients included those that recognised the S protein receptor-binding domain (RBD) and were capable of inhibiting binding to ACE-2. These data revealed events and patterns of SARS-CoV-2 seroconversion that may be important predictors of the outcome of infection and guide the delivery of clinical services in the COVID-19 response.
MeSH term(s)	Aged ; Aged, 80 and over ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/immunology ; Cohort Studies ; Coronavirus Nucleocapsid Proteins/chemistry ; Female ; Hospitalization ; Humans ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Phosphoproteins/chemistry ; SARS-CoV-2/chemistry ; Seroconversion ; Spike Glycoprotein, Coronavirus/chemistry ; Wales
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Coronavirus Nucleocapsid Proteins ; Immunoglobulin G ; Phosphoproteins ; Spike Glycoprotein, Coronavirus ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-01-26
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0245382
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Temporal development and neutralising potential of antibodies against SARS-CoV-2 in hospitalised COVID-19 patients

Isa Murrell / Donall Forde / Wioleta Zelek / Linda Tyson / Lisa Chichester / Nicki Palmer / Rachel Jones / B Paul Morgan / Catherine Moore

PLoS ONE, Vol 16, Iss 1, p e

An observational cohort study.

2021 Volume 0245382

Abstract	Antibody responses are important in the control of viral respiratory infection in the human host. What is not clear for SARS-CoV-2 is how rapidly this response occurs, or when antibodies with protective capability evolve. Hence, defining the events of SARS-CoV-2 seroconversion and the time frame for the development of antibodies with protective potential may help to explain the different clinical presentations of COVID-19. Furthermore, accurate descriptions of seroconversion are needed to inform the best use of serological assays for diagnostic testing and serosurveillance studies. Here, we describe the humoral responses in a cohort of hospitalised COVID-19 patients (n = 19) shortly following the onset of symptoms. Commercial and 'in-house' serological assays were used to measure IgG antibodies against different SARS-CoV-2 structural antigens-Spike (S) S1 sub-unit and Nucleocapsid protein (NP)-and to assess the potential for virus neutralisation mediated specifically by inhibition of binding between the viral attachment protein (S protein) and cognate receptor (ACE-2). Antibody response kinetics varied amongst the cohort, with patients seroconverting within 1 week, between 1-2 weeks, or after 2 weeks, following symptom onset. Anti-NP IgG responses were generally detected earlier, but reached maximum levels slower, than anti-S1 IgG responses. The earliest IgG antibodies produced by all patients included those that recognised the S protein receptor-binding domain (RBD) and were capable of inhibiting binding to ACE-2. These data revealed events and patterns of SARS-CoV-2 seroconversion that may be important predictors of the outcome of infection and guide the delivery of clinical services in the COVID-19 response.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
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)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: A longitudinal comparison of spike and nucleocapsid SARS-CoV-2 antibody responses in a tertiary hospitals laboratory workers with validation of DBS specimen analysis.

Murrell, Isa / Forde, Donall / Tyson, Linda / Chichester, Lisa / Garratt, Anna / Vineall, Owen / Palmer, Nicki / Jones, Rachel / Moore, Catherine

medRxiv

Keywords	covid19
Language	English
Publishing date	2020-11-03
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.10.29.20219931
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Higher Relative Viral Load Excretion Determined by Normalised Threshold Crossing Value in Acute Cases infected with the B.1.1.7 Lineage VOC 202012/01 (Using S gene target failure as a Proxy) When Compared to other Circulating Lineages in Wales

Couzens, Anastasia / Murrell, Isa / Johns, Ben / Pheasant, Kathleen / Turner, Luke / Evans, Jonathan / Moore, Catherine / Gifford, Laura

medRxiv

Abstract: Since the emergence of SARS-CoV-2, global monitoring of the virus using whole genome sequencing has identified mutations occurring across the viral genome. Whilst the majority have little impact on the virus, they are used effectively to monitor the ... ...

Abstract	Since the emergence of SARS-CoV-2, global monitoring of the virus using whole genome sequencing has identified mutations occurring across the viral genome. Whilst the majority have little impact on the virus, they are used effectively to monitor the movement of the virus globally and to inform locally on transmission chains. In late 2020, a variant of SARS-CoV-2 (B.1.1.7 - VOC 202012/01) was identified in the UK with a distinct constellation of mutations, including in the spike gene that increased transmissibility. A deletion in spike also affected one of the screening qPCR tests being used in the UK outside of Wales, causing a failure to detect the target. This quickly became a surrogate marker for the variant to allow rapid monitoring of the virus as it seeded into new regions of the UK. A screening study using this assay as a proxy marker, was undertaken to understand the prevalence of the variant in Wales. Secondary analysis of a screening qPCR targeting N and ORF and also included an endogenous control, was also performed to understand viral load excretion in those infected with the variant compared to other circulating lineages. Using a combination of analytical methods based on the Ct values of two gene targets normalised against the endogenous control, there was a difference in the excreted viral load. Those with the variant excreting more virus than those not infected with the variant. Supporting not only increased infectivity but offering a plausible reason why increased transmission was associated with this particular variant. Whilst there are limitations in this study, the method using Ct as a proxy for viral load can be used at the population level to determine differences in viral excretion kinetics associated with different variants.
Keywords	covid19
Language	English
Publishing date	2021-04-07
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.04.02.21254832
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Temporal Development and Neutralising Ability of Antibodies Against SARS-CoV-2 in Hospitalised COVID-19 Patients

Murrell, Isa Imanial / Forde, Donall / Zelek, Wioleta / Tyson, Linda / Chichester, Lisa / Palmer, Nicki / Jones, R / Morgan, B.P. / Moore, C

SSRN Electronic Journal ; ISSN 1556-5068

An Observational Cohort Study

2020

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.2139/ssrn.3666842
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Monoclonal antibodies targeting nonstructural viral antigens can activate ADCC against human cytomegalovirus.

Vlahava, Virginia-Maria / Murrell, Isa / Zhuang, Lihui / Aicheler, Rebecca J / Lim, Eleanor / Miners, Kelly L / Ladell, Kristin / Suárez, Nicolás M / Price, David A / Davison, Andrew J / Wilkinson, Gavin Wg / Wills, Mark R / Weekes, Michael P / Wang, Eddie Cy / Stanton, Richard J

The Journal of clinical investigation

2021 Volume 131, Issue 4

Abstract: Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes severe disease following congenital infection and in immunocompromised individuals. No vaccines are licensed, and there are limited treatment options. We now show that the addition of anti- ...

Abstract	Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes severe disease following congenital infection and in immunocompromised individuals. No vaccines are licensed, and there are limited treatment options. We now show that the addition of anti-HCMV antibodies (Abs) can activate NK cells prior to the production of new virions, through Ab-dependent cellular cytotoxicity (ADCC), overcoming viral immune evasins. Quantitative proteomics defined the most abundant HCMV proteins on the cell surface, and we screened these targets to identify the viral antigens responsible for activating ADCC. Surprisingly, these were not structural glycoproteins; instead, the immune evasins US28, RL11, UL5, UL141, and UL16 each individually primed ADCC. We isolated human monoclonal Abs (mAbs) specific for UL16 or UL141 from a seropositive donor and optimized them for ADCC. Cloned Abs targeting a single antigen (UL141) were sufficient to mediate ADCC against HCMV-infected cells, even at low concentrations. Collectively, these findings validated an unbiased methodological approach to the identification of immunodominant viral antigens, providing a pathway toward an immunotherapeutic strategy against HCMV and potentially other pathogens.
MeSH term(s)	Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibodies, Viral/immunology ; Antibodies, Viral/pharmacology ; Antibody-Dependent Cell Cytotoxicity/drug effects ; Antigens, Viral/immunology ; Cell Line, Transformed ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/pathology ; Humans ; Viral Nonstructural Proteins/immunology ; Virus Activation/drug effects ; Virus Activation/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Viral ; Antigens, Viral ; Viral Nonstructural Proteins
Language	English
Publishing date	2021-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI139296
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.184: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: A longitudinal comparison of spike and nucleocapsid SARS-CoV-2 antibody responses in a tertiary hospitals laboratory workers with validation of DBS specimen analysis

Murrell, Isa / Forde, Donall / Tyson, Linda / Chichester, Lisa / Garratt, Anna / Vineall, Owen / Palmer, Nicki / Jones, Rachel / Moore, Catherine

Abstract: There is a requirement for easily accessible, high throughput serological testing as part of the SARS-CoV-2 pandemic response. Whilst of limited diagnostic use in an acute individual setting, its use on a population level is key to informing a coherent ... ...

Abstract	There is a requirement for easily accessible, high throughput serological testing as part of the SARS-CoV-2 pandemic response. Whilst of limited diagnostic use in an acute individual setting, its use on a population level is key to informing a coherent public health response. As experience of commercial assays increases, so too does knowledge of their precision and limitations. Here we present our experience of these systems thus far. We perform a spot sero-prevalence study amongst staff in a tertiary hospitals clinical microbiology laboratory, before undertaking validation of DBS serological testing as an alternate specimen for analysis. Finally, we characterise the spike and nucleocapsid antibody response over 160 days post a positive PCR test in nine non-hospitalised staff members. Amongst a cohort of 195 staff, 17 tested positive for SARS-CoV-2 antibodies (8.7%). Self-reporting of SARS-CoV2 infection (P=<0.0001) and testing of a household contact (P = 0.027) were significant variables amongst the positive and negative sub-groups. Testing of 28 matched serum and DBS samples demonstrated 96% accuracy between the sample types. A differential rate of decline of SARS-CoV-2 antibodies against nucleocapsid or spike protein was observed. At 4 months post a positive PCR test 7/9 (78%) individuals had detectable antibodies against spike protein, but only 2/9 (22%) had detectable antibodies against nucleocapsid protein. This study reveals a broad agreement amongst commercial platforms tested and suggests the use of DBS as an alternate specimen option to enable widespread population testing for SARS-CoV-2 antibodies. These results suggest potential limitations of these platforms in estimating historical infection. By setting this temporal point of reference for this cohort of non-patient facing laboratory staff, future exposure risks and mitigation strategies can be evaluated more fully.
Keywords	covid19
Publisher	MedRxiv; WHO
Document type	Article ; Online
Note	WHO #Covidence: #20219931
DOI	10.1101/2020.10.29.20219931
Database	COVID19

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: The pentameric complex drives immunologically covert cell-cell transmission of wild-type human cytomegalovirus.

Murrell, Isa / Bedford, Carmen / Ladell, Kristin / Miners, Kelly L / Price, David A / Tomasec, Peter / Wilkinson, Gavin W G / Stanton, Richard J

Proceedings of the National Academy of Sciences of the United States of America

2017 Volume 114, Issue 23, Page(s) 6104–6109

Abstract: Human cytomegalovirus (HCMV) strains that have been passaged in vitro rapidly acquire mutations that impact viral growth. These laboratory-adapted strains of HCMV generally exhibit restricted tropism, produce high levels of cell-free virus, and develop ... ...

Abstract	Human cytomegalovirus (HCMV) strains that have been passaged in vitro rapidly acquire mutations that impact viral growth. These laboratory-adapted strains of HCMV generally exhibit restricted tropism, produce high levels of cell-free virus, and develop susceptibility to natural killer cells. To permit experimentation with a virus that retained a clinically relevant phenotype, we reconstructed a wild-type (WT) HCMV genome using bacterial artificial chromosome technology. Like clinical virus, this genome proved to be unstable in cell culture; however, propagation of intact virus was achieved by placing the RL13 and UL128 genes under conditional expression. In this study, we show that WT-HCMV produces extremely low titers of cell-free virus but can efficiently infect fibroblasts, epithelial, monocyte-derived dendritic, and Langerhans cells via direct cell-cell transmission. This process of cell-cell transfer required the UL128 locus, but not the RL13 gene, and was significantly less vulnerable to the disruptive effects of IFN, cellular restriction factors, and neutralizing antibodies compared with cell-free entry. Resistance to neutralizing antibodies was dependent on high-level expression of the pentameric gH/gL/gpUL128-131A complex, a feature of WT but not passaged strains of HCMV.
MeSH term(s)	Antibodies, Neutralizing ; Cell Culture Techniques/methods ; Cell Line ; Cells, Cultured ; Chromosomes, Artificial, Bacterial/metabolism ; Cytomegalovirus/genetics ; Cytomegalovirus/metabolism ; Cytomegalovirus/pathogenicity ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/metabolism ; Fibroblasts/metabolism ; Humans ; Membrane Glycoproteins/metabolism ; Mutation ; Phenotype ; Tropism/immunology ; Viral Envelope Proteins/metabolism ; Virus Internalization ; Virus Replication/immunology
Chemical Substances	Antibodies, Neutralizing ; Membrane Glycoproteins ; Viral Envelope Proteins
Language	English
Publishing date	2017-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1704809114
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Genetic Stability of Bacterial Artificial Chromosome-Derived Human Cytomegalovirus during Culture In Vitro.

Murrell, Isa / Wilkie, Gavin S / Davison, Andrew J / Statkute, Evelina / Fielding, Ceri A / Tomasec, Peter / Wilkinson, Gavin W G / Stanton, Richard J

Journal of virology

2016 Volume 90, Issue 8, Page(s) 3929–3943

Abstract: Unlabelled: Clinical human cytomegalovirus (HCMV) strains invariably mutate when propagatedin vitro Mutations in gene RL13 are selected in all cell types, whereas in fibroblasts mutants in the UL128 locus (UL128L; genes UL128, UL130, and UL131A) are ... ...

Abstract	Unlabelled: Clinical human cytomegalovirus (HCMV) strains invariably mutate when propagatedin vitro Mutations in gene RL13 are selected in all cell types, whereas in fibroblasts mutants in the UL128 locus (UL128L; genes UL128, UL130, and UL131A) are also selected. In addition, sporadic mutations are selected elsewhere in the genome in all cell types. We sought to investigate conditions under which HCMV can be propagated without incurring genetic defects. Bacterial artificial chromosomes (BACs) provide a stable, genetically defined source of viral genome. Viruses were generated from BACs containing the genomes of strains TR, TB40, FIX, and Merlin, as well as from Merlin-BAC recombinants containing variant nucleotides in UL128L from TB40-BAC4 or FIX-BAC. Propagation of viruses derived from TR-BAC, TB40-BAC4, and FIX-BAC in either fibroblast or epithelial cells was associated with the generation of defects around the prokaryotic vector, which is retained in the unique short (US) region of viruses. This was not observed for Merlin-BAC, from which the vector is excised in derived viruses; however, propagation in epithelial cells was consistently associated with mutations in the unique longb' (UL/b') region, all impacting on gene UL141. Viruses derived from Merlin-BAC in fibroblasts had mutations in UL128L, but mutations occurred less frequently with recombinants containing UL128L nucleotides from TB40-BAC4 or FIX-BAC. Viruses derived from a Merlin-BAC derivative in which RL13 and UL128L were either mutated or repressed were remarkably stable in fibroblasts. Thus, HCMV containing a wild-type gene complement can be generatedin vitroby deriving virus from a self-excising BAC in fibroblasts and repressing RL13 and UL128L. Importance: Researchers should aim to study viruses that accurately represent the causative agents of disease. This is problematic for HCMV because clinical strains mutate rapidly when propagatedin vitro, becoming less cell associated, altered in tropism, more susceptible to natural killer cells, and less pathogenic. Following isolation from clinical material, HCMV genomes can be stabilized by cloning into bacterial artificial chromosomes (BACs), and then virus is regenerated by DNA transfection. However, mutations can occur not only during isolation prior to BAC cloning but also when virus is regenerated. We have identified conditions under which BAC-derived viruses containing an intact, wild-type genome can be propagatedin vitrowith minimal risk of mutants being selected, enabling studies of viruses expressing the gene complement of a clinical strain. However, even under these optimized conditions, sporadic mutations can occur, highlighting the advisability of sequencing the HCMV stocks used in experiments.
MeSH term(s)	Cell Line ; Chromosomes, Artificial, Bacterial ; Cytomegalovirus/genetics ; Cytomegalovirus/growth & development ; Epithelial Cells ; Fibroblasts ; Genes, Viral ; Genome, Viral ; Genomic Instability ; Humans ; In Vitro Techniques ; Membrane Glycoproteins/genetics ; Viral Envelope Proteins/genetics ; Virus Cultivation/methods
Chemical Substances	Membrane Glycoproteins ; UL128 protein, human cytomegalovirus ; Viral Envelope Proteins
Language	English
Publishing date	2016-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02858-15
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 609: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Impact of sequence variation in the UL128 locus on production of human cytomegalovirus in fibroblast and epithelial cells.

Murrell, Isa / Tomasec, Peter / Wilkie, Gavin S / Dargan, Derrick J / Davison, Andrew J / Stanton, Richard J

Journal of virology

2013 Volume 87, Issue 19, Page(s) 10489–10500

Abstract: The human cytomegalovirus (HCMV) virion envelope contains a complex consisting of glycoproteins gH and gL plus proteins encoded by the UL128 locus (UL128L): pUL128, pUL130, and pUL131A. UL128L is necessary for efficient infection of myeloid, epithelial, ... ...

Abstract	The human cytomegalovirus (HCMV) virion envelope contains a complex consisting of glycoproteins gH and gL plus proteins encoded by the UL128 locus (UL128L): pUL128, pUL130, and pUL131A. UL128L is necessary for efficient infection of myeloid, epithelial, and endothelial cells but limits replication in fibroblasts. Consequently, disrupting mutations in UL128L are rapidly selected when clinical isolates are cultured in fibroblasts. In contrast, bacterial artificial chromosome (BAC)-cloned strains TB40-BAC4, FIX, and TR do not contain overt disruptions in UL128L, yet no virus reconstituted from them has been reported to acquire mutations in UL128L in vitro. We performed BAC mutagenesis and reconstitution experiments to test the hypothesis that these strains contain subtle mutations in UL128L that were acquired during passage prior to BAC cloning. Compared to strain Merlin containing wild-type UL128L, all three strains produced higher yields of cell-free virus. Moreover, TB40-BAC4 and FIX spread cell to cell more rapidly than wild-type Merlin in fibroblasts but more slowly in epithelial cells. The differential growth properties of TB40-BAC4 and FIX (but not TR) were mapped to single-nucleotide substitutions in UL128L. The substitution in TB40-BAC4 reduced the splicing efficiency of UL128, and that in FIX resulted in an amino acid substitution in UL130. Introduction of these substitutions into Merlin dramatically increased yields of cell-free virus and increased cell-to-cell spread in fibroblasts but reduced the abundance of pUL128 in the virion and the efficiency of epithelial cell infection. These substitutions appear to represent mutations in UL128L that permit virus to be propagated in fibroblasts while retaining epithelial cell tropism.
MeSH term(s)	Blotting, Western ; Cells, Cultured ; Chromosomes, Artificial, Bacterial/genetics ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/genetics ; Cytomegalovirus Infections/metabolism ; Cytomegalovirus Infections/virology ; Endothelial Cells/metabolism ; Endothelial Cells/virology ; Fetus ; Fibroblasts/metabolism ; Fibroblasts/virology ; Foreskin/metabolism ; Foreskin/virology ; Genetic Variation ; Humans ; Male ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Mutagenesis ; Mutation/genetics ; Plasmids/genetics ; Retinal Pigment Epithelium/metabolism ; Retinal Pigment Epithelium/virology ; Tropism ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/metabolism ; Virion/physiology ; Virus Internalization
Chemical Substances	Membrane Glycoproteins ; UL128 protein, human cytomegalovirus ; Viral Envelope Proteins
Language	English
Publishing date	2013-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01546-13
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 609: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

Kategorien

Inter-library loan at ZB MED

Full text online

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito