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Article ; Online: Imaging cytomegalovirus infection and ensuing immune responses.

Bošnjak, Berislav / Lueder, Yvonne / Messerle, Martin / Förster, Reinhold

2023 Volume 82, Page(s) 102307

Abstract: Cytomegaloviruses (CMVs) possess exquisite mechanisms enabling colonization, replication, and release allowing spread to new hosts. Moreover, they developed ways to escape the control of the host immune responses and hide latently within the host cells. ... ...

Abstract	Cytomegaloviruses (CMVs) possess exquisite mechanisms enabling colonization, replication, and release allowing spread to new hosts. Moreover, they developed ways to escape the control of the host immune responses and hide latently within the host cells. Here, we outline studies that visualized individual CMV-infected cells using reporter viruses. These investigations provided crucial insights into all steps of CMV infection and mechanisms the host's immune response struggles to control it. Uncovering complex viral and cellular interactions and underlying molecular as well as immunological mechanisms are a prerequisite for the development of novel therapeutic interventions for successful treatment of CMV-related pathologies in neonates and transplant patients.
MeSH term(s)	Infant, Newborn ; Humans ; Cytomegalovirus Infections ; Cytomegalovirus ; Immunity
Language	English
Publishing date	2023-03-28
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2023.102307
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Article ; Online: NK cell dysfunction in severe COVID-19: TGF-β-induced downregulation of integrin beta-2 restricts NK cell cytotoxicity.

Barros-Martins, Joana / Förster, Reinhold / Bošnjak, Berislav

Signal transduction and targeted therapy

2022 Volume 7, Issue 1, Page(s) 32

MeSH term(s)	COVID-19 ; Down-Regulation ; Humans ; Integrins ; Killer Cells, Natural ; SARS-CoV-2 ; Transforming Growth Factor beta
Chemical Substances	Integrins ; Transforming Growth Factor beta
Language	English
Publishing date	2022-01-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2886872-9
ISSN	2059-3635 ; 2095-9907
ISSN (online)	2059-3635
ISSN	2095-9907
DOI	10.1038/s41392-022-00892-5
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Article ; Online: Hide and seek with SARS-CoV-2: spike receptor-binding domain-specific memory B cells still recognize Omicron variant.

Odak, Ivan / Förster, Reinhold / Bošnjak, Berislav

Signal transduction and targeted therapy

2022 Volume 7, Issue 1, Page(s) 343

MeSH term(s)	COVID-19 ; Humans ; Memory B Cells ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/genetics
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-10-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2886872-9
ISSN	2059-3635 ; 2095-9907
ISSN (online)	2059-3635
ISSN	2095-9907
DOI	10.1038/s41392-022-01192-8
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Article ; Online: Challenges of CRISPR-Based Gene Editing in Primary T Cells.

Rezalotfi, Alaleh / Fritz, Lea / Förster, Reinhold / Bošnjak, Berislav

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Adaptive T-cell immunotherapy holds great promise for the successful treatment of leukemia, as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. ...

Abstract	Adaptive T-cell immunotherapy holds great promise for the successful treatment of leukemia, as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T-cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system, allowing for the deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs that were important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.
MeSH term(s)	CRISPR-Cas Systems ; Gene Editing/methods ; Humans ; Immunotherapy ; T-Lymphocytes
Language	English
Publishing date	2022-02-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031689
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Article ; Online: NK cell dysfunction in severe COVID-19

Joana Barros-Martins / Reinhold Förster / Berislav Bošnjak

Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-

TGF-β-induced downregulation of integrin beta-2 restricts NK cell cytotoxicity

2022 Volume 3

Keywords	Medicine ; R ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Challenges of CRISPR-Based Gene Editing in Primary T Cells

Alaleh Rezalotfi / Lea Fritz / Reinhold Förster / Berislav Bošnjak

International Journal of Molecular Sciences, Vol 23, Iss 1689, p

2022 Volume 1689

Abstract	Adaptive T-cell immunotherapy holds great promise for the successful treatment of leukemia, as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T-cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system, allowing for the deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs that were important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.
Keywords	adoptive T-cell therapy ; CAR T cells ; CRISPR/Cas9 ; gene modifications ; T cells ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Imaging dendritic cell functions.

Bošnjak, Berislav / Do, Kim Thi Hoang / Förster, Reinhold / Hammerschmidt, Swantje I

Immunological reviews

2021 Volume 306, Issue 1, Page(s) 137–163

Abstract: Dendritic cells (DCs) are crucial for the appropriate initiation of adaptive immune responses. During inflammation, DCs capture antigens, mature, and migrate to lymphoid tissues to present foreign material to naïve T cells. These cells get activated and ... ...

Abstract	Dendritic cells (DCs) are crucial for the appropriate initiation of adaptive immune responses. During inflammation, DCs capture antigens, mature, and migrate to lymphoid tissues to present foreign material to naïve T cells. These cells get activated and differentiate either into pathogen-specific cytotoxic CD8
MeSH term(s)	Antigen Presentation ; CD8-Positive T-Lymphocytes ; Dendritic Cells ; Humans ; Immune Tolerance ; T-Lymphocytes, Cytotoxic
Language	English
Publishing date	2021-12-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13050
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Article ; Online: MCK2-mediated MCMV infection of macrophages and virus dissemination to the salivary gland depends on MHC class I molecules.

Bošnjak, Berislav / Henze, Elisa / Lueder, Yvonne / Do, Kim Thi Hoang / Rezalotfi, Alaleh / Čuvalo, Berislav / Ritter, Christiane / Schimrock, Anja / Willenzon, Stefanie / Georgiev, Hristo / Fritz, Lea / Galla, Melanie / Wagner, Karen / Messerle, Martin / Förster, Reinhold

Cell reports

2023 Volume 42, Issue 6, Page(s) 112597

Abstract: Murine cytomegalovirus (MCMV) infection of macrophages relies on MCMV-encoded chemokine 2 (MCK2), while infection of fibroblasts occurs independently of MCK2. Recently, MCMV infection of both cell types was found to be dependent on cell-expressed ... ...

Abstract	Murine cytomegalovirus (MCMV) infection of macrophages relies on MCMV-encoded chemokine 2 (MCK2), while infection of fibroblasts occurs independently of MCK2. Recently, MCMV infection of both cell types was found to be dependent on cell-expressed neuropilin 1. Using a CRISPR screen, we now identify that MCK2-dependent infection requires MHC class Ia/β-2-microglobulin (B2m) expression. Further analyses reveal that macrophages expressing MHC class Ia haplotypes H-2b and H-2d, but not H-2k, are susceptible to MCK2-dependent infection with MCMV. The importance of MHC class I expression for MCK2-dependent primary infection and viral dissemination is highlighted by experiments with B2m-deficient mice, which lack surface expression of MHC class I molecules. In those mice, intranasally administered MCK2-proficient MCMV mimics infection patterns of MCK2-deficient MCMV in wild-type mice: it does not infect alveolar macrophages and subsequently fails to disseminate into the salivary glands. Together, these data provide essential knowledge for understanding MCMV-induced pathogenesis, tissue targeting, and virus dissemination.
MeSH term(s)	Mice ; Animals ; Muromegalovirus ; Histocompatibility Antigens Class I ; Cytomegalovirus Infections ; Macrophages ; Salivary Glands ; Mice, Inbred BALB C
Chemical Substances	Histocompatibility Antigens Class I
Language	English
Publishing date	2023-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112597
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Article ; Online: The effect of Toll-like receptor agonists on the immunogenicity of MVA-SARS-2-S vaccine after intranasal administration in mice.

Do, Kim Thi Hoang / Willenzon, Stefanie / Ristenpart, Jasmin / Janssen, Anika / Volz, Asisa / Sutter, Gerd / Förster, Reinhold / Bošnjak, Berislav

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1259822

Abstract: Background and aims: Modified Vaccinia virus Ankara (MVA) represents a promising vaccine vector for respiratory administration to induce protective lung immunity including tertiary lymphoid structure, the bronchus-associated lymphoid tissue (BALT). ... ...

Abstract	Background and aims: Modified Vaccinia virus Ankara (MVA) represents a promising vaccine vector for respiratory administration to induce protective lung immunity including tertiary lymphoid structure, the bronchus-associated lymphoid tissue (BALT). However, MVA expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein (MVA-SARS-2-S) required prime-boost administration to induce high titers of anti-Spike antibodies in serum and bronchoalveolar lavage (BAL). As the addition of adjuvants enables efficient tailoring of the immune responses even to live vaccines, we tested whether Toll-like receptor (TLR)-agonists affect immune responses induced by a single dose of intranasally applied MVA-SARS-2-S. Methods: We intranasally immunized C57BL/6 mice with MVA-SARS-2-S vaccine in the presence of either TLR3 agonist polyinosinic polycytidylic acid [poly(I:C)], TLR4 agonist bacterial lipopolysaccharide (LPS) from Results: TLR agonists had profound effects on MVA-SARS-2-S-induced immune responses. At day 1 post intranasal application, the TLR4 agonist significantly affected MVA-induced activation of dendritic cells (DCs) within the draining bronchial lymph nodes, increasing the ratio of CD11b Conclusions: Our study indicates a potential role of TLR-agonists as a tool to modulate immune responses to live vector vaccines. Particularly TLR3 agonists hold a promise to potentiate MVA-induced cellular immune responses. On the other hand, additional research is necessary to identify optimal combinations of agonists that could enhance MVA-induced humoral responses.
MeSH term(s)	Animals ; Mice ; SARS-CoV-2 ; Administration, Intranasal ; CD8-Positive T-Lymphocytes ; Toll-Like Receptor 3 ; Toll-Like Receptor 4 ; Toll-Like Receptor 9 ; Mice, Inbred C57BL ; COVID-19/prevention & control ; Vaccinia virus ; Adjuvants, Immunologic ; Vaccines ; Antibodies, Viral
Chemical Substances	Toll-Like Receptor 3 ; Toll-Like Receptor 4 ; Toll-Like Receptor 9 ; Adjuvants, Immunologic ; Vaccines ; Antibodies, Viral
Language	English
Publishing date	2023-10-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1259822
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Article ; Online: MCK2-mediated MCMV infection of macrophages and virus dissemination to the salivary gland depends on MHC class I molecules

Berislav Bošnjak / Elisa Henze / Yvonne Lueder / Kim Thi Hoang Do / Alaleh Rezalotfi / Berislav Čuvalo / Christiane Ritter / Anja Schimrock / Stefanie Willenzon / Hristo Georgiev / Lea Fritz / Melanie Galla / Karen Wagner / Martin Messerle / Reinhold Förster

Cell Reports, Vol 42, Iss 6, Pp 112597- (2023)

2023

Abstract: Summary: Murine cytomegalovirus (MCMV) infection of macrophages relies on MCMV-encoded chemokine 2 (MCK2), while infection of fibroblasts occurs independently of MCK2. Recently, MCMV infection of both cell types was found to be dependent on cell- ... ...

Abstract	Summary: Murine cytomegalovirus (MCMV) infection of macrophages relies on MCMV-encoded chemokine 2 (MCK2), while infection of fibroblasts occurs independently of MCK2. Recently, MCMV infection of both cell types was found to be dependent on cell-expressed neuropilin 1. Using a CRISPR screen, we now identify that MCK2-dependent infection requires MHC class Ia/β-2-microglobulin (B2m) expression. Further analyses reveal that macrophages expressing MHC class Ia haplotypes H-2b and H-2d, but not H-2k, are susceptible to MCK2-dependent infection with MCMV. The importance of MHC class I expression for MCK2-dependent primary infection and viral dissemination is highlighted by experiments with B2m-deficient mice, which lack surface expression of MHC class I molecules. In those mice, intranasally administered MCK2-proficient MCMV mimics infection patterns of MCK2-deficient MCMV in wild-type mice: it does not infect alveolar macrophages and subsequently fails to disseminate into the salivary glands. Together, these data provide essential knowledge for understanding MCMV-induced pathogenesis, tissue targeting, and virus dissemination.
Keywords	CP: Immunology ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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