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Article ; Online: Noncognate Signals Drive Enhanced Effector CD8

Gmyrek, Grzegorz B / Predki, Paul / Gershburg, Edward / Carr, Daniel J J

2022 Volume 96, Issue 6, Page(s) e0172421

Abstract: Previous studies by our group identified a highly efficacious vaccine 0ΔNLS (deficient in the nuclear localization signal of infected cell protein 0) against herpes simplex virus 1 (HSV-1) in an experimental ocular mouse model. However, details regarding ...

Abstract	Previous studies by our group identified a highly efficacious vaccine 0ΔNLS (deficient in the nuclear localization signal of infected cell protein 0) against herpes simplex virus 1 (HSV-1) in an experimental ocular mouse model. However, details regarding fundamental differences in the initial innate and adaptive host immune response were not explored. Here, we present a side-by-side analysis of the primary infection characterizing differences of the host immune response in mice infected with 0ΔNLS versus the parental, GFP105. The results show that local viral infection and replication are controlled more efficiently in mice exposed to 0ΔNLS versus GFP105 but that the clearance of infectious virus is equivalent when the two groups are compared. Moreover, the 0ΔNLS-infected mice displayed enhanced effector CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Herpes Simplex/immunology ; Herpes Simplex Virus Vaccines/immunology ; Herpesvirus 1, Human ; Interferon-gamma/immunology ; Mice ; Mice, Inbred C57BL ; Receptor, Interferon alpha-beta/immunology
Chemical Substances	Herpes Simplex Virus Vaccines ; Ifnar1 protein, mouse ; Receptor, Interferon alpha-beta (156986-95-7) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.01724-21
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over Time.

Carr, Daniel J J / Berube, Amanda / Gershburg, Edward

Pathogens (Basel, Switzerland)

2021 Volume 10, Issue 11

Abstract: Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or ... ...

Abstract	Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25-50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to short-term studies in a conventional prime-boost protocol.
Language	English
Publishing date	2021-11-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens10111470
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Article ; Online: Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses.

Stanfield, Brent A / Kousoulas, Konstantin G / Fernandez, Agustin / Gershburg, Edward

Viruses

2021 Volume 13, Issue 8

Abstract: Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses ... ...

Abstract	Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed "latency", which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines' "rational" design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.
MeSH term(s)	Animals ; Drug Design ; Herpes Simplex/immunology ; Herpes Simplex/prevention & control ; Herpes Simplex/virology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/immunology ; Herpesvirus 2, Human/genetics ; Herpesvirus 2, Human/immunology ; Humans ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology ; Viral Vaccines/administration & dosage ; Viral Vaccines/immunology
Chemical Substances	Vaccines, Attenuated ; Viral Vaccines
Language	English
Publishing date	2021-08-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13081637
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Article ; Online: The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over Time

Daniel J. J. Carr / Amanda Berube / Edward Gershburg

Pathogens, Vol 10, Iss 1470, p

2021 Volume 1470

Abstract	Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25–50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to ...
Keywords	herpes simplex virus type 1 ; cornea ; vaccine ; neovascularization ; visual acuity ; Medicine ; R
Subject code	630 ; 570
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over Time

Carr, Daniel J. J. / Berube, Amanda / Gershburg, Edward

Pathogens. 2021 Nov. 12, v. 10, no. 11

2021

Abstract	Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25–50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to short-term studies in a conventional prime-boost protocol.
Keywords	Human alphaherpesvirus 1 ; blood ; cornea ; durability ; laboratory animals ; opacity ; vaccination ; vaccines ; virus replication ; viruses
Language	English
Dates of publication	2021-1112
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens10111470
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Molecular diversity of IgG responses to Epstein-Barr virus proteins in asymptomatic Epstein-Barr virus carriers.

Goswami, Ria / Shair, Kathy Ho Yen / Gershburg, Edward

The Journal of general virology

2017 Volume 98, Issue 9, Page(s) 2343–2350

Abstract: The Epstein-Barr virus (EBV) is a ubiquitous pathogen that infects over 90 % of adults. EBV is the primary etiological agent of infectious mononucleosis and is closely associated with nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma and ... ...

Abstract	The Epstein-Barr virus (EBV) is a ubiquitous pathogen that infects over 90 % of adults. EBV is the primary etiological agent of infectious mononucleosis and is closely associated with nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma and Burkitt lymphoma. Clinical serological assays for EBV diagnosis only survey a small portion of the viral proteome, which does not represent the total antigenic breadth presented to the immune system during viral infection. In this study, we have generated an expression library containing the majority of EBV ORFs, and have systematically evaluated IgG responses to those EBV proteins in sera from EBV carriers. In addition to confirming previously recognized dominant EBV antigens, this study has identified additional immunodominant antigens, and has revealed a more expansive antigenic profile of the humoral responses to EBV in asymptomatic carriers. This EBV expression library will be deposited in a public repository with the goal of disseminating this new research tool for the application of identifying potential new biomarkers for EBV-associated diseases.
MeSH term(s)	Antibodies, Viral/immunology ; Antigens, Viral/genetics ; Antigens, Viral/immunology ; Asymptomatic Diseases ; Carrier State/immunology ; Carrier State/virology ; Epstein-Barr Virus Infections/immunology ; Epstein-Barr Virus Infections/virology ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/immunology ; Herpesvirus 4, Human/isolation & purification ; Humans ; Immunoglobulin G/immunology
Chemical Substances	Antibodies, Viral ; Antigens, Viral ; Immunoglobulin G
Language	English
Publishing date	2017-08-10
Publishing country	England
Document type	Journal Article
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.000891
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs.

Joyce, Jonathan D / Patel, Anant K / Murphy, Brandie / Carr, Daniel J J / Gershburg, Edward / Bertke, Andrea S

Vaccines

2021 Volume 9, Issue 3

Abstract: Treatment to ameliorate the symptoms of infection with herpes simplex virus 2 (HSV-2) and to suppress reactivation has been available for decades. However, a safe and effective preventative or therapeutic vaccine has eluded development. Two novel live- ... ...

Abstract	Treatment to ameliorate the symptoms of infection with herpes simplex virus 2 (HSV-2) and to suppress reactivation has been available for decades. However, a safe and effective preventative or therapeutic vaccine has eluded development. Two novel live-attenuated HSV-2 vaccine candidates (RVx201 and RVx202) have been tested preclinically for safety. Hartley guinea pigs were inoculated vaginally (
Language	English
Publishing date	2021-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9030258
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Article: Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses

Stanfield, Brent A. / Kousoulas, Konstantin G. / Fernandez, Agustin / Gershburg, Edward

Viruses. 2021 Aug. 18, v. 13, no. 8

2021

Abstract	Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed “latency”, which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines’ “rational” design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.
Keywords	DNA ; direct contact ; encephalitis ; herpes simplex ; human diseases ; humans ; influenza ; keratitis ; live vaccines ; measles ; medical history ; smallpox ; socioeconomics ; transcription (genetics) ; vaccination ; virus transmission ; viruses
Language	English
Dates of publication	2021-0818
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13081637
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens of a live-attenuated HSV-2 vaccine.

Geltz, Joshua J / Gershburg, Edward / Halford, William P

PloS one

2015 Volume 10, Issue 2, Page(s) e0116091

Abstract: Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected ... ...

Abstract	Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748). In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens) of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Immunoprecipitation (IP) of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2's thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine's capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.
MeSH term(s)	Animals ; Antigens, Viral/genetics ; Antigens, Viral/metabolism ; Herpes Genitalis/prevention & control ; Herpes Simplex Virus Vaccines/genetics ; Herpes Simplex Virus Vaccines/immunology ; Herpesvirus 2, Human/metabolism ; Immunoglobulin G/blood ; Immunoprecipitation ; Mass Spectrometry ; Mice ; Viral Envelope Proteins/metabolism
Chemical Substances	Antigens, Viral ; Herpes Simplex Virus Vaccines ; Immunoglobulin G ; Viral Envelope Proteins ; glycoprotein D-herpes simplex virus type 2
Language	English
Publishing date	2015-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0116091
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The UL13 and US3 Protein Kinases of Herpes Simplex Virus 1 Cooperate to Promote the Assembly and Release of Mature, Infectious Virions.

Gershburg, Svetlana / Geltz, Joshua / Peterson, Karin E / Halford, William P / Gershburg, Edward

PloS one

2015 Volume 10, Issue 6, Page(s) e0131420

Abstract: Herpes simplex virus type 1 (HSV-1) encodes two bona fide serine/threonine protein kinases, the US3 and UL13 gene products. HSV-1 ΔUS3 mutants replicate with wild-type efficiency in cultured cells, and HSV-1 ΔUL13 mutants exhibit <10-fold reduction in ... ...

Abstract	Herpes simplex virus type 1 (HSV-1) encodes two bona fide serine/threonine protein kinases, the US3 and UL13 gene products. HSV-1 ΔUS3 mutants replicate with wild-type efficiency in cultured cells, and HSV-1 ΔUL13 mutants exhibit <10-fold reduction in infectious viral titers. Given these modest phenotypes, it remains unclear how the US3 and UL13 protein kinases contribute to HSV-1 replication. In the current study, we designed a panel of HSV-1 mutants, in which portions of UL13 and US3 genes were replaced by expression cassettes encoding mCherry protein or green fluorescent protein (GFP), respectively, and analyzed DNA replication, protein expression, and spread of these mutants in several cell types. Loss of US3 function alone had largely negligible effect on viral DNA accumulation, gene expression, virion release, and spread. Loss of UL13 function alone also had no appreciable effects on viral DNA levels. However, loss of UL13 function did result in a measurable decrease in the steady-state levels of two viral glycoproteins (gC and gD), release of total and infectious virions, and viral spread. Disruption of both genes did not affect the accumulation of viral DNA, but resulted in further reduction in gC and gD steady-state levels, and attenuation of viral spread and infectious virion release. These data show that the UL13 kinase plays an important role in the late phase of HSV-1 infection, likely by affecting virion assembly and/or release. Moreover, the data suggest that the combined activities of the US3 and UL13 protein kinases are critical to the efficient assembly and release of infectious virions from HSV-1-infected cells.
MeSH term(s)	Animals ; Cells, Cultured ; Cercopithecus aethiops ; Herpes Simplex/genetics ; Herpes Simplex/pathology ; Herpes Simplex/virology ; Humans ; Mutant Proteins/genetics ; Mutant Proteins/physiology ; Protein Kinases/genetics ; Protein Kinases/physiology ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/physiology ; Vero Cells ; Viral Proteins/genetics ; Viral Proteins/physiology ; Virus Assembly/genetics ; Virus Shedding/genetics
Chemical Substances	Mutant Proteins ; Viral Proteins ; Protein Kinases (EC 2.7.-) ; UL13 protein, Simplexvirus (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; US3 protein, Human herpesvirus 1 (EC 2.7.11.1)
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0131420
Database	MEDical Literature Analysis and Retrieval System OnLINE

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