Sidney E. Grossberg, PhDSidney E. Grossberg, MD

Professor
Microbiology and Molecular Genetics
Medical College of Wisconsin

Research Focus: Studies of Interferons and Retroviruses

MD: Emory University (1954)


Our current research deals with the molecular, immunological, and biological characterization of a new human RNA virus that replicates in human B-lymphoblastoid cells. The virus, designated JHKV, is an enveloped, relatively fragile particle containing RNA, reverse transcriptase, and prominent, knobbed glycoprotein projections. Although the JHK virus resembles a retrovirus (but 35% smaller than most other retroviruses), it is clearly not like any of the known human retroviruses (human immunodeficiency virus or human T-lymphotropic virus), as determined either by polymerase chain reactions or electron microscopy. The JHK-3 B-lymphoblastoid cell line that constitutively produces the JHK virus (and the Epstein-Barr virus as well) has the antigenic markers of immature B-lymphocytes by flow cytometry. cDNA libraries produced by reverse transcription of JHK viral RNA have been constructed and are being analyzed; the sequences determined of the many clones produced have so far revealed no significant homology with known viruses.  Polyclonal antibodies and certain monoclonal antibodies we have produced react with JHKV by enzyme-linked immunosorbent assay, Western immunoblot, and immunogold binding, like sera from certain patients. The possible etiological role of the JHK virus in diseases that may involve B-lymphocytes, such as leukemia, lymphoma, chronic fatigue syndrome or immune dysfunction states, remains to be determined. The goals of current experimental studies are to (i) clone, sequence, and map the viral genome; (ii) characterize monoclonal antibodies to the virus; (iii) identify viral antigens; and (iv) develop methods to detect JHKV infection, using nucleic acid probes for hybridization and primers for the polymerase chain reaction.

Sidney E. Grossberg, MD

Recent Publications

Grossberg SE, Kawade Y, Grossberg LD.  The Neutralization of Interferons by Antibody III.  The Constant Antibody Bioassay, A Highly Sensitive Quantitative Detector of Low Antibody Levels.  J Interferon Cytokine Res.  Epub 2008 Nov 11.
Abstract

Lallemand C, Meritet JF, Erickson R, Grossberg SE, Roullet E, Lyon-Caen O, Lebon P, Tovey MG.  Quantification of neutralizing antibodies to human type I interferons using division-arrested frozen cells carrying an interferon-regulated reporter-gene.  J Interferon Cytokine Res.  2008 Jun;28(6):393-404.
Abstract

Boz C, Oger J, Gibbs E, Grossberg SE; Neurologists of the UBC MS Clinic.  Reduced effectiveness of long-term interferon-beta treatment on relapses in neutralizing antibody-positive multiple sclerosis patients: a Canadian multiple sclerosis clinic-based study.  Mult Scler.  2007 Nov;13(9):1127-37.
Abstract

Sun HY, McNally MT, Jackson VE, Grossberg SE.  Urea-nuclease treatment of concentrated retrovirions preserves viral RNA and removes polymerase chain reaction-amplifiable cellular RNA and DNA.  J Virol Methods.  2006 Nov;137(2):304-8.  Epub 2006 Aug 21.
Abstract

Joklik WK, Grossberg SE.  How the American Society for Virology was Founded.  Virology.  2006 Jan 5;344(1):250-7.
Abstract

Mildvan D, Spritzler J, Grossberg SE, Fahey JL, Johnston DM, Schock BR, Kagan J.  Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection.  Clin Infect Dis.  2005 Mar 15;40(6):853-8.  Epub 2005 Feb 18.
Abstract

Grossberg SE.  Perspectives on the neutralization of interferons by antibody.  Neurology.  2003 Nov 11;61(9 Suppl 5):S21-3.  Review.
Abstract

Kawade Y, Finter N, Grossberg SE.  Neutralization of the biological activity of cytokines and other protein effectors by antibody: theoretical formulation of antibody titration curves in relation to antibody affinity.  J Immunol Methods.  2003 Jul;278(1-2):127-44.
Abstract

Wolinsky JS, Toyka KV, Kappos L, Grossberg SE.  Interferon-beta antibodies: implications for the treatment of MS.  Lancet Neurol.  2003 Sep;2(9):528.  Review.
Abstract

Raisch KP, Pizzato M, Sun HY, Takeuchi Y, Cashdollar LW, Grossberg SE.  Molecular cloning, complete sequence, and biological characterization of a xenotropic murine leukemia virus constitutively released from the human B-lymphoblastoid cell line DG-75.  Virology.  2003 Mar 30;308(1):83-91.
Abstract

Runkel L, De Dios C, Karpusas M, Baker D, Li Z, Zafari M, Betzenhauser M, Muldowney C, Miller S, Redlich PN, Grossberg SE, Whitty A, Hochman PS.  Mapping of IFN-beta epitopes important for receptor binding and biologic activation: comparison of results achieved using antibody-based methods and alanine substitution mutagenesis.  J Interferon Cytokine Res.  2001 Nov;21(11):931-41.
Abstract

Grossberg SE, Kawade Y, Kohase M, Klein JP.  The neutralization of interferons by antibody. II. Neutralizing antibody unitage and its relationship to bioassay sensitivity: the tenfold reduction unit.  J Interferon Cytokine Res.  2001 Sep;21(9):743-55.
Abstract

Grossberg SE, Kawade Y, Kohase M, Yokoyama H, Finter N.  The neutralization of interferons by antibody. I. Quantitative and theoretical analyses of the neutralization reaction in different bioassay systems.  J Interferon Cytokine Res.  2001 Sep;21(9):729-42.
Abstract

Osorio JE, Grossberg SE, Palmenberg AC.  Characterization of genetically engineered mengoviruses in mice.  Viral Immunol.  2000;13(1):27-35.
Abstract

Golgher RR, Redlich PN, Totti DO, Grossberg SE.  Quantitative liquid-phase chemiluminescence ELISA: detection of subtle epitope differences in HuIFN-beta.  J Interferon Cytokine Res.  1999 Sep;19(9):995-8.
Abstract

Contact Information
Please call the Microbiology Department office for contact information at (414) 955-8253.

Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226
(414) 955-8296
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