Eva Szomolanyi-tsuda - Academia.edu (original) (raw)

Papers by Eva Szomolanyi-tsuda

Development of long-term humoral immunity is a major goal of vaccination, but the mechanisms invo... more Development of long-term humoral immunity is a major goal of vaccination, but the mechanisms involved in the formation of long-term Ab responses are still being determined. In this study, we identify a previously unknown requirement for MyD88, an adaptor molecule that mediates signals at most TLRs, for the generation of long-term humoral immunity during live virus infection. Polyoma virus-infected MyD88

Nature, Jan 19, 2001

Considerable progress has been made in identifying the transcription factors involved in the earl... more Considerable progress has been made in identifying the transcription factors involved in the early specification of the B-lymphocyte lineage. However, little is known about factors that control the transition of mature activated B cells to antibody-secreting plasma cells. Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. XBP-1 transcripts were rapidly upregulated in vitro by stimuli that induce plasma-cell differentiation, and were found at high levels in plasma cells from rheumatoid synovium. When introduced into B-lineage cells, XBP-1 initiated plasma-cell differentiation. Mouse lymphoid chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes that proliferated, secreted cytokines and formed normal germinal centres. However, they secreted very little immunoglobulin of any isotype and failed to control infection with the B-cell-dependent polyoma virus, because plasma cells were markedly absent. XBP-1 is the on...

Journal of virology, 1998

Immunoglobulin G (IgG) responses to viruses are generally assumed to be T-cell dependent (TD). Re... more Immunoglobulin G (IgG) responses to viruses are generally assumed to be T-cell dependent (TD). Recently, however, polyomavirus (PyV) infection of T-cell-deficient (T-cell receptor beta chain [TCR-beta] -/- or TCR-betaxdelta -/-) mice was shown to elicit a protective, T-cell-independent (TI) antiviral IgM and IgG response. A repetitive, highly organized antigenic structure common to many TI antigens is postulated to be important in the induction of antibody responses in the absence of helper T cells. To test whether the repetitive structure of viral antigens is essential and/or sufficient for the induction of TI antibodies, we compared the abilities of three forms of PyV antigens to induce IgM and IgG responses in T-cell-deficient mice: soluble capsid antigens (VP1), repetitive virus-like particles (VLPs), and live PyV. Immunization with each of the viral antigens resulted in IgM production. VLPs and PyV elicited 10-fold-higher IgM titers than VP1, indicating that the highly organize...

Critical Reviews in Oncogenesis, 2014

Natural killer (NK) cells become activated during viral infections and can play roles in such inf... more Natural killer (NK) cells become activated during viral infections and can play roles in such infections by attacking virus-infected cells or by regulating adaptive immune responses. Experimental models suggest that NK cells may also have the capacity to restrain virus-induced cancers. Here, we discuss the seven viruses linked to human cancers and the evidence of NK cell involvement in these systems.

Virology, 2006

IgM and IgG antibody responses in T cell-deficient mice, but these responses are not generated by... more IgM and IgG antibody responses in T cell-deficient mice, but these responses are not generated by immunization with viral proteins or virus like particles. We hypothesized that innate signals contribute to the generation of isotype-switched antiviral antibody responses. We studied the role of complement receptor (CR2) engagement in TI and T celldependent (TD) antibody responses to PyV using CR2-deficient mice. Antiviral IgG responses were reduced by 80-40% in CR2−/− mice compared to wild type. Adoptive transfer experiments demonstrated the need for CR2 not only in TD, but also in TI IgG responses to PyV. Transfer of CR2−/− B lymphocytes to SCID mice resulted in TI antiviral IgG responses that corresponded to 10% of that seen in wild-type B cellreconstituted mice. Thus, our studies revealed a profound dependence of TI and TD antiviral antibody responses on CR2-mediated signals in PyVinfected mice, where the viral antigen is abundant and persistent.

Virology, 2001

in T-cell-deficient (TCR ␤x␦Ϫ/Ϫ) mice. In this study, we show that PyV is a TI -2 antigen: B cell... more in T-cell-deficient (TCR ␤x␦Ϫ/Ϫ) mice. In this study, we show that PyV is a TI -2 antigen: B cells with a mutated Bruton's tyrosine kinase (Xid mutants) do not respond to PyV with antibody secretion in the absence of T cells. We also demonstrate that NK-cell-mediated "help" is not absolutely required for the induction of the TI-2 antibodies to PyV; thus for the first time, we provide evidence for protective IgM and IgG responses against a viral infection induced in mice lacking T and NK cells (CD3Etg). Comparison of the antibody responses observed in T-and NK-cell-deficient mice with those of mice lacking only T cells, however, suggests that NK cells may promote isotype switching to IgG2a. This effect is probably mediated by IFN␥ secretion. In support of this idea, studies on the antibody responses of PyV-infected SCID mice that had been reconstituted with IFN␥RϪ/Ϫ B cells or wild-type B cells demonstrated the IFN␥ dependence of PyV-specific TI IgG2a secretion and provided evidence that IFN␥ acting directly on B cells plays an important role in TI pathways of isotype switching to IgG2a in vivo.

PLoS Pathogens, 2012

Most DNA viruses replicate in the cell nucleus, although the specific sites of virion assembly ar... more Most DNA viruses replicate in the cell nucleus, although the specific sites of virion assembly are as yet poorly defined. Electron microscopy on freeze-substituted, plastic-embedded sections of murine polyomavirus (PyV)-infected 3T3 mouse fibroblasts or mouse embryonic fibroblasts (MEFs) revealed tubular structures in the nucleus adjacent to clusters of assembled virions, with virions apparently ''shed'' or ''budding'' from their ends. Promyelocytic leukemia nuclear bodies (PML-NBs) have been suggested as possible sites for viral replication of polyomaviruses (BKV and SV40), herpes simplex virus (HSV), and adenovirus (Ad). Immunohistochemistry and FISH demonstrated co-localization of the viral T-antigen (Tag), PyV DNA, and the host DNA repair protein MRE11, adjacent to the PML-NBs. In PML 2/2 MEFs the co-localization of MRE11, Tag, and PyV DNA remained unchanged, suggesting that the PML protein itself was not responsible for their association. Furthermore, PyV-infected PML 2/2 MEFs and PML 2/2 mice replicated wild-type levels of infectious virus. Therefore, although the PML protein may identify sites of PyV replication, neither the observed ''virus factories'' nor virus assembly were dependent on PML. The ultrastructure of the tubes suggests a new model for the encapsidation of small DNA viruses.

Nature Immunology, 2002

ABSTRACT Functionally active inhibitory receptors that impart negative signals have been found re... more ABSTRACT Functionally active inhibitory receptors that impart negative signals have been found recently on T cells. One such inhibitory receptor, CD94-NKG2A, can induce cytolytic anergy in CTLs specific for polyomavirus.

The Journal of Immunology, 2001

The Journal of Immunology, 2009

Journal of Clinical Investigation, 2004

The production of protective neutralizing antibodies occurs quickly in some viral infections but ... more The production of protective neutralizing antibodies occurs quickly in some viral infections but very slowly in others. In a new study, surface glycoproteins (the targets of neutralization) of 2 different viruses were genetically switched. Analysis of the neutralizing antibody response to each of the 2 parent and recombinant viruses in infected mice revealed that the speed of neutralizing antibody induction was intrinsically dependent on the surface glycoprotein and not the rest of the virus (see the related article beginning on page 988). Nonstandard abbreviations used: AID, activationinduced deaminase; LCMV, lymphocytic choriomeningitis virus; rLCMV, recombinant LCMV; rLCMV/ VSV-GP, rLCMV expressing VSV-glycoprotein; rVSV, recombinant VSV; rVSV/LCMV-GP, rVSV expressing LCMV-glycoprotein; SIV, simian immunodeficiency virus; VSV, vesicular stomatitis virus.

Annual Review of Immunology, 2004

The purpose of immunological memory is to protect the host from reinfection, to control persisten... more The purpose of immunological memory is to protect the host from reinfection, to control persistent infections, and, through maternal antibody, to protect the host's immunologically immature offspring from primary infections. Immunological memory is an exclusive property of the acquired immune system, where in the presence of CD4 T cell help, T cells and B cells clonally expand and differentiate to provide effector systems that protect the host from pathogens. Here we describe how T and B cell memory is generated in response to virus infections and how these cells respond when the host is infected again by similar or different viruses.

Journal of Immunology, 2013

Infections with DNA tumor viruses, including members of the polyomavirus family, often result in ... more Infections with DNA tumor viruses, including members of the polyomavirus family, often result in tumor formation in immune-deficient hosts. The complex control involved in antiviral and antitumor immune responses during these infections can be studied in murine polyomavirus (PyV)-infected mice as a model. We found that NK cells efficiently kill cells derived from PyV-induced salivary gland tumors in vitro in an NKG2D (effector cell)-RAE-1 (target cell)-dependent manner; but in T cell-deficient mice, NK cells only delay but do not prevent the development of PyV-induced tumors. In this article, we show that the PyV-induced tumors have infiltrating functional NK cells. The freshly removed tumors, however, lack surface RAE-1 expression, and the tumor tissues produce soluble factors that downregulate RAE-1. These factors include the proinflammatory cytokines IL-1α, IL-1β, IL-33, and TNF. Each of these cytokines downregulates RAE-1 expression and susceptibility to NK cell-mediated cytotoxicity. CD11b(+)F4/80(+) macrophages infiltrating the PyV-induced tumors produce high amounts of IL-1β and TNF. Thus, our data suggest a new mechanism whereby inflammatory cytokines generated in the tumor environment lead to evasion of NK cell-mediated control of virus-induced tumors.

Nature Immunology, 2010

Optimal protection from infection requires complex immune responses involving both the innate and... more Optimal protection from infection requires complex immune responses involving both the innate and adaptive immune systems. The innate immune system has a key role in initiating and orchestrating host defenses by regulating the production of proinflammatory cytokines, type I interferons and antimicrobial effectors 1 . Several distinct classes of germline-encoded pattern-recognition receptors have been discovered and have been linked to the sensing of microbial products. These include the Toll-like receptors (TLRs) 2 , the C-type lectin receptors 3 , the RIG-like helicases 4 , the Nod-like receptors (NLRs) 5 , and the cytosolic DNA sensors DAI 6 , RNA polymerase III (refs. 7,8) and . These receptors recognize microbial products from bacteria, viruses, fungi and parasites and in most cases trigger signaling pathways that culminate in the transcription of genes involved in the immune response 1 .