Susan Michelson
Pasteur Institute
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Featured researches published by Susan Michelson.
Journal of Clinical Investigation | 1999
Julie Déchanet; Pierre Merville; Annick Lim; Christelle Retière; Vincent Pitard; Xavier Lafarge; Susan Michelson; Claude Meric; Marie-Martine Hallet; Philippe Kourilsky; L. Potaux; Marc Bonneville; Jean-François Moreau
In normal individuals, γδ T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vδ2-Vγ9 chains. We have previously observed a dramatic expansion of γδ T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection. This increase was long lasting (more than 1 year), was associated with an activation of γδ T cells, and concerned only Vδ1 or Vδ3 T-cell subpopulations. Analysis of γδ TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vδ3 and, to a lesser extent, in Vδ1 chains; and (b) a selective expansion of Vδ1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of γδ T-cell subsets during the course of CMV infection. Furthermore, Vδ1 and Vδ3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus–infected fibroblast lysates. This in vitro expansion was inhibited by anti-γδ TCR mAb’s. These findings suggest that a population of γδ T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.
The Journal of Infectious Diseases | 2001
Klara Berencsi; Zsofia Gyulai; Eva Gönczöl; Steve Pincus; William I. Cox; Susan Michelson; Laszlo Kari; Claude Meric; Michel Cadoz; John Zahradnik; Stuart E. Starr; Stanley Plotkin
The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8(+). Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.
Journal of Virology | 2001
Patrick S. Beisser; Lysiane Laurent; Jean-Louis Virelizier; Susan Michelson
ABSTRACT The human cytomegalovirus (HCMV) US28 gene product, pUS28, is a G protein-coupled receptor that interacts with both CC and CX3C chemokines. To date, the role of pUS28 in immune evasion and cell migration has been studied only in cell types that can establish productive HCMV infection. We show that HCMV can latently infect THP-1 monocytes and that during latency US28 is transcribed. We also show that the transcription is sustained during differentiation of the THP-1 monocytes. Since cells expressing pUS28 were previously shown to adhere to immobilized CX3C chemokines (C. A. Haskell, M. D. Cleary, and I. F. Charo, J. Biol. Chem. 275:34183–34189, 2000), we hypothesize that latently infected circulating monocytes express pUS28, thereby enabling adhesion of these cells to CX3C-exposing endothelium. Consequently, the US28-encoded chemokine receptor may play an important role in dissemination of latent HCMV.
British Journal of Ophthalmology | 2006
I De Schryver; Flore Rozenberg; Nathalie Cassoux; Susan Michelson; Philippe Kestelyn; Phuc LeHoang; Jl Davis; Bahram Bodaghi
Aim: To describe the diagnostic and therapeutic management of cytomegalovirus (CMV) anterior uveitis unassociated with retinal necrosis in immunocompetent patients. Methods: Patients referred between 2001 and 2003 for management of unilateral, chronic, recurrent uveitis associated with secondary glaucoma underwent extensive investigation including laboratory tests for herpes virus infections. Specific antiviral treatment was initiated in all cases and the level of ocular inflammation was evaluated during the follow up. Results: Five patients, three men and two women, were included. Median age was 50 years old (range 30–80 years). Anterior unilateral uveitis without iris atrophy was observed in all cases. Uveitis was chronic in three cases and recurrent in two cases. Glaucoma was observed in all patients with a median intraocular pressure of 30 mm Hg (range 22–43 mm Hg). Five patients responded initially to specific anti-CMV therapy. Even though glaucoma surgery was necessary in two cases, both ocular inflammation and glaucoma were controlled in all cases. Relapses occurred in three cases after cessation of therapy, requiring prolonged maintenance therapy with valganciclovir. Conclusions: CMV infection and specific antiviral therapy should be considered in all cases of relapsing or chronic iridocyclitis and secondary glaucoma. Maintenance regimens of valganciclovir may be necessary to prevent further relapses.
Antiviral Research | 2001
Luigi Buonaguro; Franco M. Buonaguro; Maria Lina Tornesello; D. Mantas; Elke Beth-Giraldo; Ralf Wagner; Susan Michelson; M.-C. Prevost; Hans Wolf; Gaetano Giraldo
The main goal of this study was to investigate a novel approach for an efficient and reproducible production of Virus-Like Particles (VLPs) expressing multiple HIV-1 epitopes. The HIV-1 Pr55(gag)-based VLPs have been produced in a Baculovirus expression system, using a transfer vector able to support the independent expression of different open reading frames (ORFs). In this regard, the gp120 derived from 94UG018 HIV-1(A) isolate, previously studied in our laboratory, has been packaged into the VLPs together with nef and pol ORFs. In particular, the gp120(UG) sequence shows a 90% homology in the V3 region compared to African HIV-1 strains of the A-clade. This novel approach is extremely effective for the production of VLPs expressing all the epitopes, as confirmed by Western Blot characterization. Furthermore, the resulting HIV-VLP(A)s show the expected density (1.14--1.18 g/ml) on a 10--60% sucrose gradient and the morphology of an immature virion at standard transmission electron microscopy. Our results demonstrate that this strategy is highly efficient for expressing a balanced amount of multiple epitopes and their packaging in VLP structures, without affecting the Pr55(gag) autoassembling capacities. Furthermore, the genetic transposition performed in a modified E. coli represents a methodological improvement, allowing a faster and more reproducible identification of recombinant Baculovirus DNA molecules.
FEBS Letters | 1983
Octavian Bârzu; Susan Michelson
Adenylate kinase from E. coli (strains CR341 and CR341 T28, a temperature‐sensitive mutant) was purified by a two‐step chromatographic procedure. The enzyme from crude extracts of both mutant and parent strain was bound to blue—Sepharose at pH 7.5, thereafter specifically eluted with 0.05 mM P 1,P 5‐di(adenosine‐5′)pentaphosphate. A second chromatography on Sephadex G‐100 yielded pure enzyme. E. coli adenylate kinase was strongly inhibited by P 1,P 5‐di(adenosine‐5′)pentaphosphate (K i 0.6 μM for adenylate kinase of strain CR341 and 2.1 μM in the case of mutant enzyme). After denaturation in 6 M guanidinium hydrochloride both mutant and parent adenylate kinase returned rapidly to the native, active state by dilution of guanidinium hydrochloride.
FEBS Journal | 2005
Olivier Pleskoff; Paola Casarosa; L. Verneuil; Fadela Aïnoun; Patrick S. Beisser; Martine J. Smit; Rob Leurs; Pascal Schneider; Susan Michelson; Jean Claude Ameisen
Viral subversion of apoptosis regulation plays an important role in the outcome of host/virus interactions. Although human cytomegalovirus (HCMV) encodes several immediate early (IE) antiapoptotic proteins (IE1, IE2, vMIA and vICA), no proapoptotic HCMV protein has yet been identified. Here we show that US28, a functional IE HCMV‐encoded chemokine receptor, which may be involved in both viral dissemination and immune evasion, constitutively induces apoptosis in several cell types. In contrast, none of nine human cellular chemokine receptors, belonging to three different subfamilies, induced any significant level of apoptosis. US28‐induced cell death involves caspase 10 and caspase 8 activation, but does not depend on the engagement of cell‐surface death receptors of the tumour necrosis factor receptor/CD95 family. US28 cell‐death induction is prevented by coexpression of C‐FLIP, a protein that inhibits Fas‐associated death domain protein (FADD)‐mediated activation of caspase 10 and caspase 8, and by coexpression of the HCMV antiapoptotic protein IE1. The use of US28 mutants indicated that the DRY sequence of its third transmenbrane domain, required for constitutive G‐protein signalling, and the US28 intracellular terminal domain required for constitutive US28 endocytosis, are each partially required for cell‐death induction. Thus, in HCMV‐infected cells, US28 may function either as a chemokine receptor, a phospholipase C activator, or a proapoptotic factor, depending on expression levels of HCMV and/or cellular antiapoptotic proteins.
Journal of General Virology | 1991
José Alcami; Térèsa Barzu; Susan Michelson
Human cytomegalovirus (HCMV) induction of growth factors in fibroblasts was investigated after establishing serum-free culture conditions conducive to viral replication. HCMV infection induced a type II heparin-binding growth factor which stimulated human endothelial cell proliferation.
Scandinavian Journal of Immunology | 1995
Jean-Luc Davignon; D. Clément; J. Alriquet; Susan Michelson; Christian Davrinche
Cellular immune responses are important in the recovery from human cytomegalovirus (HCMV) infection. However, little is known about the CD4+ T cell response and the target antigens (Ag) recognized. In this paper, we have analysed the proliferative T cell response of healthy HCMV seropositive (HCMV+) blood donors to recombinant immediate‐early proteins expressed in trans‐fected astrocytoma cells and to total HCMV Ags expressed in infected astrocytoma cells. We found that CD4+ T cells were the major cell population that proliferated in the presence of IE or total HCMV Ags. Among healthy HCMV seropositive blood donors with anti‐HCMV specific proliferative response, 33–44% also responded to IE Ags. Moreover, in high responders, the precursor frequencies of cells which proliferated in the presence of total HCMV, IE, or IEl Ags were high (1/103 to 1/255, 1/2785 to 1/7744 and 1/5190 to 1/13531, respectively). In some donors, the anti‐IE response was variable over time, whereas the anti‐total HCMV Ags response remained constant, which suggests regulation of the anti‐IE response in immunocompetent subjects. Our results suggest that the CD4+ anti‐IEl response represents a significant part of the anti‐HCMV proliferative response, both at the population level, and within individual immune systems.
Intervirology | 1999
Susan Michelson
Human cytomegalovirus (CMV) has devised numerous means of escaping immune surveillance. The CMV genome encodes at least 4 genes involved in downregulating surface expression of HLA class I molecules. In addition, it sequesters CC chemokines, induces Fc receptors, interferes with induction of HLA class II antigens, and can inhibit natural killer cell activity. CMV can efficiently block the presentation of immediate early antigens, the first viral proteins to be produced. Together, these mechanisms probably contribute to the ability of CMV to persist in its host and may play a role in the immunopathology of CMV disease.