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Article ; Online: Cell-to-cell spread inhibiting antibodies constitute a correlate of protection against herpes simplex virus type 1 reactivations: A retrospective study.

Alt, Mira / Wolf, Susanne / van de Sand, Lukas / Dittrich, Robin / Tertel, Tobias / Brochhagen, Leonie / Dirks, Miriam / Aufderhorst, Ulrich Wilhelm / Thümmler, Laura / Otte, Mona / Rainer, Kordula / Dittmer, Ulf / Giebel, Bernd / Trilling, Mirko / Silke Heilingloh, Christiane / Lotfi, Ramin / Roggendorf, Michael / Witzke, Oliver / Krawczyk, Adalbert

Frontiers in immunology

2023 Volume 14, Page(s) 1143870

Abstract: Background: Herpes simplex viruses (HSV) cause ubiquitous human infections. For vaccine development, knowledge concerning correlates of protection is essential. Therefore, we investigated (I) if humans are in principle capable producing cell-to-cell ... ...

Abstract	Background: Herpes simplex viruses (HSV) cause ubiquitous human infections. For vaccine development, knowledge concerning correlates of protection is essential. Therefore, we investigated (I) if humans are in principle capable producing cell-to-cell spread inhibiting antibodies against HSV and (II) whether this capacity is associated with a reduced HSV-1 reactivation risk. Methods: We established a high-throughput HSV-1-ΔgE-GFP reporter virus-based assay and evaluated 2,496 human plasma samples for HSV-1 glycoprotein E (gE) independent cell-to-cell spread inhibiting antibodies. Subsequently, we conducted a retrospective survey among the blood donors to analyze the correlation between the presence of cell-to-cell spread inhibiting antibodies in plasma and the frequency of HSV reactivations. Results: In total, 128 of the 2,496 blood donors (5.1%) exhibited high levels of HSV-1 gE independent cell-to-cell spread inhibiting antibodies in the plasma. None of the 147 HSV-1 seronegative plasmas exhibited partial or complete cell-to-cell spread inhibition, demonstrating the specificity of our assay. Individuals with cell-to-cell spread inhibiting antibodies showed a significantly lower frequency of HSV reactivations compared to subjects without sufficient levels of such antibodies. Conclusion: This study contains two important findings: (I) upon natural HSV infection, some humans produce cell-to-cell spread inhibiting antibodies and (II) such antibodies correlate with protection against recurrent HSV-1. Moreover, these elite neutralizers may provide promising material for immunoglobulin therapy and information for the design of a protective vaccine against HSV-1.
MeSH term(s)	Humans ; Herpesvirus 1, Human ; Retrospective Studies ; Viral Envelope Proteins ; Herpes Simplex ; Immunization, Passive ; Antibodies, Blocking
Chemical Substances	Viral Envelope Proteins ; Antibodies, Blocking
Language	English
Publishing date	2023-03-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1143870
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Article ; Online: Antiviral Active Compounds Derived from Natural Sources against Herpes Simplex Viruses.

van de Sand, Lukas / Bormann, Maren / Schmitz, Yasmin / Heilingloh, Christiane Silke / Witzke, Oliver / Krawczyk, Adalbert

Viruses

2021 Volume 13, Issue 7

Abstract: Herpes simplex viruses (HSV) are ubiquitously distributed with a seroprevalence ranging up to 95% in the adult population. Refractory viral infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) represent a major global health issue. In ... ...

Abstract	Herpes simplex viruses (HSV) are ubiquitously distributed with a seroprevalence ranging up to 95% in the adult population. Refractory viral infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) represent a major global health issue. In particular, the increasing occurrence of resistance to conventional antiviral drugs make the therapy of such infections even more challenging. For instance, the frequent and long-term use of acyclovir and other nucleoside analogues targeting the viral DNA-polymerase enhance the development of resistant viruses. Particularly, the incidental increase of those strains in immunocompromised patients is alarming and represent a major health concern. Alternative treatment concepts are clearly needed. Natural products such as herbal medicines showed antiherpetic activity in vitro and in vivo and proved to be an excellent source for the discovery and isolation of novel antivirals. By this means, numerous plant-derived compounds with antiviral or antimicrobial activity could be isolated. Natural medicines and their ingredients are well-tolerated and could be a good alternative for treating herpes simplex virus infections. This review provides an overview of the recent status of natural sources such as plants, bacteria, fungi, and their ingredients with antiviral activity against herpes simplex viruses. Furthermore, we highlight the most potent herbal medicines and ingredients as promising candidates for clinical investigation and give an overview about the most important drug classes along with their potential antiviral mechanisms. The content of this review is based on articles that were published between 1996 and 2021.
MeSH term(s)	Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Biological Products/chemistry ; Biological Products/pharmacology ; Biological Products/therapeutic use ; Clinical Trials as Topic ; Herpes Simplex/drug therapy ; Herpes Simplex/virology ; Humans ; Mice ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Plants, Medicinal/chemistry ; Simplexvirus/classification ; Simplexvirus/drug effects
Chemical Substances	Antiviral Agents ; Biological Products ; Plant Extracts
Language	English
Publishing date	2021-07-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071386
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Article: Antiviral Active Compounds Derived from Natural Sources against Herpes Simplex Viruses

van de Sand, Lukas / Bormann, Maren / Schmitz, Yasmin / Heilingloh, Christiane Silke / Witzke, Oliver / Krawczyk, Adalbert

Viruses. 2021 July 16, v. 13, no. 7

2021

Abstract	Herpes simplex viruses (HSV) are ubiquitously distributed with a seroprevalence ranging up to 95% in the adult population. Refractory viral infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) represent a major global health issue. In particular, the increasing occurrence of resistance to conventional antiviral drugs make the therapy of such infections even more challenging. For instance, the frequent and long-term use of acyclovir and other nucleoside analogues targeting the viral DNA-polymerase enhance the development of resistant viruses. Particularly, the incidental increase of those strains in immunocompromised patients is alarming and represent a major health concern. Alternative treatment concepts are clearly needed. Natural products such as herbal medicines showed antiherpetic activity in vitro and in vivo and proved to be an excellent source for the discovery and isolation of novel antivirals. By this means, numerous plant-derived compounds with antiviral or antimicrobial activity could be isolated. Natural medicines and their ingredients are well-tolerated and could be a good alternative for treating herpes simplex virus infections. This review provides an overview of the recent status of natural sources such as plants, bacteria, fungi, and their ingredients with antiviral activity against herpes simplex viruses. Furthermore, we highlight the most potent herbal medicines and ingredients as promising candidates for clinical investigation and give an overview about the most important drug classes along with their potential antiviral mechanisms. The content of this review is based on articles that were published between 1996 and 2021.
Keywords	Human alphaherpesvirus 1 ; adults ; antiviral agents ; antiviral properties ; herpes simplex ; nucleosides ; seroprevalence ; therapeutics ; viruses
Language	English
Dates of publication	2021-0716
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071386
Database	NAL-Catalogue (AGRICOLA)

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Article: Mass Spectrometric Characterization of HSV-1 L-Particles From Human Dendritic Cells and BHK21 Cells and Analysis of Their Functional Role.

Birzer, Alexandra / Kraner, Max Edmund / Heilingloh, Christiane Silke / Mühl-Zürbes, Petra / Hofmann, Jörg / Steinkasserer, Alexander / Popella, Linda

Frontiers in microbiology

2020 Volume 11, Page(s) 1997

Abstract: Herpes simplex virus type 1 (HSV-1) is a very common human pathogenic virus among the world's population. The lytic replication cycle of HSV-1 is, amongst others, characterized by a tripartite viral gene expression cascade, the assembly of nucleocapsids ... ...

Abstract	Herpes simplex virus type 1 (HSV-1) is a very common human pathogenic virus among the world's population. The lytic replication cycle of HSV-1 is, amongst others, characterized by a tripartite viral gene expression cascade, the assembly of nucleocapsids involving their subsequent nuclear egress, tegumentation, re-envelopment and the final release of progeny viral particles. During productive infection of a multitude of different cell types, HSV-1 generates not only infectious heavy (H-) particles, but also non-infectious light (L-) particles, lacking the capsid. In monocyte-derived mature dendritic cells (mDCs), HSV-1 causes a non-productive infection with the predominant release of L-particles. Until now, the generation and function of L-particles is not well understood, however, they are described as factors transferring viral components to the cellular microenvironment. To obtain deeper insights into the L-particle composition, we performed a mass-spectrometry-based analysis of L-particles derived from HSV-1-infected mDCs or BHK21 cells and H-particles from the latter one. In total, we detected 63 viral proteins in both H- and L-particle preparations derived from HSV-1-infected BHK21 cells. In L-particles from HSV-1-infected mDCs we identified 41 viral proteins which are differentially distributed compared to L-particles from BHK21 cells. In this study, we present data suggesting that L-particles modify mDCs and suppress their T cell stimulatory capacity. Due to the plethora of specific viral proteins incorporated into and transmitted by L-particles, it is tempting to speculate that L-particles manipulate non-infected bystander cells for the benefit of the virus.
Language	English
Publishing date	2020-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2020.01997
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Article ; Online: PGAM5-MAVS interaction regulates TBK1/ IRF3 dependent antiviral responses.

Yu, Yu-Qiang / Zielinska, Marta / Li, Wei / Bernkopf, Dominic B / Heilingloh, Christiane Silke / Neurath, Markus F / Becker, Christoph

Scientific reports

2020 Volume 10, Issue 1, Page(s) 8323

Abstract: Viral infections trigger host innate immune responses, characterized by the production of type-I interferons (IFN) including IFNβ. IFNβ induces cellular antiviral defense mechanisms and thereby contributes to pathogen clearance. Accumulating evidence ... ...

Abstract	Viral infections trigger host innate immune responses, characterized by the production of type-I interferons (IFN) including IFNβ. IFNβ induces cellular antiviral defense mechanisms and thereby contributes to pathogen clearance. Accumulating evidence suggests that mitochondria constitute a crucial platform for the induction of antiviral immunity. Here we demonstrate that the mitochondrial protein phosphoglycerate mutase family member 5 (PGAM5) is important for the antiviral cellular response. Following challenge of HeLa cells with the dsRNA-analog poly(I:C), PGAM5 oligomers and high levels of PGAM5 were found in mitochondrial aggregates. Using immunoprecipitation, a direct interaction of PGAM5 with the mitochondrial antiviral-signaling protein (MAVS) was demonstrated. In addition, PGAM5 deficient cells showed diminished expression of IFNβ and IFNβ target genes as compared to WT cells. Moreover, PGAM5 deficient mouse embryonic fibroblasts (MEFs) exhibited decreased phosphorylation levels of IRF3 and TBK1 when challenged with poly(I:C) intracellularly. Finally, PGAM5 deficient MEFs, upon infection with vesicular stomatitis virus (VSV), revealed diminished IFNβ expression and increased VSV replication. Collectively, our study highlights PGAM5 as an important regulator for IFNβ production mediated via the TBK1/IRF3 signaling pathway in response to viral infection.
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cells, Cultured ; Fibroblasts/virology ; HeLa Cells ; Humans ; Interferon Regulatory Factor-3/metabolism ; Interferon-beta/metabolism ; Mice ; Mitochondrial Proteins/immunology ; Mitochondrial Proteins/metabolism ; Phosphoprotein Phosphatases/immunology ; Phosphoprotein Phosphatases/metabolism ; Poly I-C/immunology ; Protein-Serine-Threonine Kinases/metabolism ; Rhabdoviridae Infections/immunology ; Signal Transduction ; Vesicular stomatitis Indiana virus/immunology ; Virus Replication/immunology
Chemical Substances	Adaptor Proteins, Signal Transducing ; IRF3 protein, human ; Interferon Regulatory Factor-3 ; MAVS protein, human ; Mitochondrial Proteins ; Interferon-beta (77238-31-4) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TBK1 protein, human (EC 2.7.11.1) ; PGAM5 protein, human (EC 3.1.3.16) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Poly I-C (O84C90HH2L)
Language	English
Publishing date	2020-05-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-65155-1
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Article ; Online: HSV-1 Modulates IL-6 Receptor Expression on Human Dendritic Cells.

Birzer, Alexandra / Krawczyk, Adalbert / Draßner, Christina / Kuhnt, Christine / Mühl-Zürbes, Petra / Heilingloh, Christiane Silke / Steinkasserer, Alexander / Popella, Linda

Frontiers in immunology

2020 Volume 11, Page(s) 1970

Abstract: Dendritic cells (DCs) are the guardians of the immune system since they are located in the majority of peripheral tissues. In addition, they are crucial for the induction of an effective immune response based on their unique capacity to stimulate naive T ...

Abstract	Dendritic cells (DCs) are the guardians of the immune system since they are located in the majority of peripheral tissues. In addition, they are crucial for the induction of an effective immune response based on their unique capacity to stimulate naive T cells. During co-evolution, the human pathogen herpes simplex virus type 1 (HSV-1) has evolved several immune evasion mechanisms in order to subvert the host's immune system especially by targeting DC biology and function. Here we demonstrate that HSV-1 infection influences the IL-6 receptor (IL6R) expression both on protein and mRNA levels in/on human monocyte-derived mature DCs (mDCs). Surprisingly, reduced IL6R expression levels were also observed on uninfected bystander mDCs. Mechanistically, we clearly show that HSV-1-derived non-infectious light (L-) particles are sufficient to trigger IL6R regulation on uninfected bystander mDCs. These L-particles lack the viral DNA-loaded capsid and are predominantly produced during infection of mDCs. Our results show that the deletion of the HSV-1 tegument protein vhs partially rescued the reduced IL6R surface expression levels on/in bystander mDCs. Using a neutralizing antibody, which perturbs the transfer of L-particles to bystander mDCs, was sufficient to rescue the modulation of IL6R surface expression on uninfected bystander mDCs. This study provides evidence that L-particles transfer specific viral proteins to uninfected bystander mDCs, thereby negatively interfering with their IL6R expression levels, however, to a lesser extend compared to H-particles. Due to their immune-modulatory capacity, L-particles represent an elaborated approach of HSV-1-mediated immune evasion.
MeSH term(s)	Biomarkers ; Bystander Effect ; Cells, Cultured ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Gene Expression Regulation ; Herpes Simplex/genetics ; Herpes Simplex/immunology ; Herpes Simplex/metabolism ; Herpes Simplex/virology ; Herpesvirus 1, Human/isolation & purification ; Herpesvirus 1, Human/physiology ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunomodulation ; Monocytes/immunology ; Monocytes/metabolism ; RNA, Messenger/genetics ; Receptors, Interleukin-6/genetics ; Receptors, Interleukin-6/metabolism ; Virus Replication
Chemical Substances	Biomarkers ; RNA, Messenger ; Receptors, Interleukin-6
Language	English
Publishing date	2020-08-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.01970
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Article ; Online: Herpes Simplex Virus Type-2 Paralyzes the Function of Monocyte-Derived Dendritic Cells.

Grosche, Linda / Mühl-Zürbes, Petra / Ciblis, Barbara / Krawczyk, Adalbert / Kuhnt, Christine / Kamm, Lisa / Steinkasserer, Alexander / Heilingloh, Christiane Silke

Viruses

2020 Volume 12, Issue 1

Abstract: Herpes simplex viruses not only infect a variety of different cell types, including dendritic cells (DCs), but also modulate important cellular functions in benefit of the virus. Given the relevance of directed immune cell migration during the initiation ...

Abstract	Herpes simplex viruses not only infect a variety of different cell types, including dendritic cells (DCs), but also modulate important cellular functions in benefit of the virus. Given the relevance of directed immune cell migration during the initiation of potent antiviral immune responses, interference with DC migration constitutes a sophisticated strategy to hamper antiviral immunity. Notably, recent reports revealed that HSV-1 significantly inhibits DC migration in vitro. Thus, we aimed to investigate whether HSV-2 also modulates distinct hallmarks of DC biology. Here, we demonstrate that HSV-2 negatively interferes with chemokine-dependent in vitro migration capacity of mature DCs (mDCs). Interestingly, rather than mediating the reduction of the cognate chemokine receptor expression early during infection, HSV-2 rapidly induces β2 integrin (LFA-1)-mediated mDC adhesion and thereby blocks mDC migration. Mechanistically, HSV-2 triggers the proteasomal degradation of the negative regulator of β2 integrin activity, CYTIP, which causes the constitutive activation of LFA-1 and thus mDC adhesion. In conclusion, our data extend and strengthen recent findings reporting the reduction of mDC migration in the context of a herpesviral infection. We thus hypothesize that hampering antigen delivery to secondary lymphoid organs by inhibition of mDC migration is an evolutionary conserved strategy among distinct members of Herpesviridae.
MeSH term(s)	Cell Adhesion ; Cell Movement ; Cells, Cultured ; Dendritic Cells/pathology ; Dendritic Cells/virology ; Guanine Nucleotide Exchange Factors/genetics ; Guanine Nucleotide Exchange Factors/immunology ; Herpesvirus 2, Human/immunology ; Herpesvirus 2, Human/pathogenicity ; Humans ; Lymphocyte Function-Associated Antigen-1/immunology ; Lymphocyte Function-Associated Antigen-1/metabolism ; Receptors, Chemokine/genetics ; Receptors, Chemokine/immunology ; Transcription Factors/genetics ; Transcription Factors/immunology ; Viral Proteins/genetics
Chemical Substances	CYTIP protein, human ; Guanine Nucleotide Exchange Factors ; Lymphocyte Function-Associated Antigen-1 ; Receptors, Chemokine ; Transcription Factors ; Viral Proteins ; cytohesin-1
Language	English
Publishing date	2020-01-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12010112
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease.

van de Sand, Lukas / Bormann, Maren / Alt, Mira / Schipper, Leonie / Heilingloh, Christiane Silke / Steinmann, Eike / Todt, Daniel / Dittmer, Ulf / Elsner, Carina / Witzke, Oliver / Krawczyk, Adalbert

Viruses

2021 Volume 13, Issue 4

Abstract: The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds ...

Abstract	The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are still urgently needed. Complementary medicine is used along with standard medical treatment and accessible to a vast majority of people worldwide. Natural products with antiviral activity may contribute to improve the overall condition of SARS-CoV-2 infected individuals. In the present study, we investigated the antiviral activity of glycyrrhizin, the primary active ingredient of the licorice root, against SARS-CoV-2. We demonstrated that glycyrrhizin potently inhibits SARS-CoV-2 replication in vitro. Furthermore, we uncovered the underlying mechanism and showed that glycyrrhizin blocks the viral replication by inhibiting the viral main protease M
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; COVID-19 ; Cell Survival/drug effects ; Chlorocebus aethiops ; Coronavirus 3C Proteases/drug effects ; Glycyrrhiza/chemistry ; Glycyrrhizic Acid/pharmacology ; Humans ; Peptide Hydrolases/drug effects ; Plant Extracts/pharmacology ; Plant Roots/chemistry ; Protease Inhibitors/pharmacology ; SARS-CoV-2/drug effects ; Vero Cells ; Virus Replication/drug effects
Chemical Substances	Antiviral Agents ; Plant Extracts ; Protease Inhibitors ; Glycyrrhizic Acid (6FO62043WK) ; Peptide Hydrolases (EC 3.4.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2021-04-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13040609
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Article: Herpes Simplex Virus Type-2 Paralyzes the Function of Monocyte-Derived Dendritic Cells

Grosche, Linda / Mühl-Zürbes, Petra / Ciblis, Barbara / Krawczyk, Adalbert / Kuhnt, Christine / Kamm, Lisa / Steinkasserer, Alexander / Heilingloh, Christiane Silke

Viruses. 2020 Jan. 16, v. 12, no. 1

2020

Abstract	Herpes simplex viruses not only infect a variety of different cell types, including dendritic cells (DCs), but also modulate important cellular functions in benefit of the virus. Given the relevance of directed immune cell migration during the initiation of potent antiviral immune responses, interference with DC migration constitutes a sophisticated strategy to hamper antiviral immunity. Notably, recent reports revealed that HSV-1 significantly inhibits DC migration in vitro. Thus, we aimed to investigate whether HSV-2 also modulates distinct hallmarks of DC biology. Here, we demonstrate that HSV-2 negatively interferes with chemokine-dependent in vitro migration capacity of mature DCs (mDCs). Interestingly, rather than mediating the reduction of the cognate chemokine receptor expression early during infection, HSV-2 rapidly induces β2 integrin (LFA-1)-mediated mDC adhesion and thereby blocks mDC migration. Mechanistically, HSV-2 triggers the proteasomal degradation of the negative regulator of β2 integrin activity, CYTIP, which causes the constitutive activation of LFA-1 and thus mDC adhesion. In conclusion, our data extend and strengthen recent findings reporting the reduction of mDC migration in the context of a herpesviral infection. We thus hypothesize that hampering antigen delivery to secondary lymphoid organs by inhibition of mDC migration is an evolutionary conserved strategy among distinct members of Herpesviridae.
Keywords	CD18 antigen ; Human alphaherpesvirus 2 ; adhesion ; cell movement ; chemokine receptors ; dendritic cells ; herpes simplex ; immune response ; lymphatic system ; viruses
Language	English
Dates of publication	2020-0116
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12010112
Database	NAL-Catalogue (AGRICOLA)

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Article: Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1.

Silke Heilingloh, Christiane / Lull, Christopher / Kleiser, Elissa / Alt, Mira / Schipper, Leonie / Witzke, Oliver / Trilling, Mirko / Eis-Hübinger, Anna-Maria / Dittmer, Ulf / Krawczyk, Adalbert

Vaccines

2020 Volume 8, Issue 3

Abstract: Infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are a global health burden. Besides painful oral or genital lesions in otherwise healthy subjects, both viruses can cause devastating morbidity and mortality in immune-compromised and ...

Abstract	Infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are a global health burden. Besides painful oral or genital lesions in otherwise healthy subjects, both viruses can cause devastating morbidity and mortality in immune-compromised and immune-immature individuals. The latter are particularly susceptible to a disseminated, life-threatening disease. Neutralizing antibodies (NAb) constitute a correlate of protection from disease, and are promising candidates for the prophylactic or therapeutic treatment of severe HSV infections. However, a clinical vaccine trial suggested that HSV-2 might be more resistant to NAbs than HSV-1. In the present study, we investigated the antiviral efficacy of the well-characterized humanized monoclonal antibody (mAb) hu2c against HSV-2, in a NOD/SCID immunodeficiency mouse model. Despite the fact that hu2c recognizes a fully conserved epitope and binds HSV-1 and HSV-2 glycoprotein B with equal affinity, it was much less effective against HSV-2 in vitro and in NOD/SCID mice. Although intravenous antibody treatment prolonged the survival of HSV-2-infected mice, complete protection from death was not achieved. Our data demonstrate that HSV-2 is more resistant to NAbs than HSV-1, even if the same antibody and antigen are concerned, making the development of a vaccine or therapeutic antibodies more challenging.
Language	English
Publishing date	2020-08-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines8030478
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