Abstract

Production of murine monoclonal antibodies to human cell surface proteins has resulted in the definition of several virus receptors on the surface of human cells. Some of these proteins are important in the function of T and B cells. CR2 has been identified as the EBV receptor, CD4 as the HIV receptor and ICAM-1 as the major rhinovirus receptor. Echoviruses (members of the human picornavirus family) are non-enveloped RNA viruses which cause aseptic meningitis in adults and fetal disseminated infections in neonates. For other picornaviruses, tissue tropism and the spectrum of clinical illness is determined by tissue expression of specific receptors for virus attachment. Receptors for echoviruses have not been defined. We have produced murine monoclonal antibodies, directed against human cell surface components, that block echovirus attachment. These antibodies immunoprecipitate human cell surface proteins of 125 and 145 Kd. We will use these antibodies and others to define the human echovirus receptor. Candidate receptor proteins will be biochemically characterized, cloned and expressed in mammalian cells to examine their ability to mediate virus attachment and internalization. These studies will allow for the development of animal models of disease and characterization of the function of the cell protein(s) involved in binding.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI031628-02
Application #
3146681
Study Section
Experimental Immunology Study Section (EI)
Project Start
1992-03-01
Project End
1995-02-28
Budget Start
1993-03-01
Budget End
1994-02-28
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Finberg, Robert W; Re, Fabio; Popova, Lana et al. (2004) Cell activation by Toll-like receptors: role of LBP and CD14. J Endotoxin Res 10:413-8
Kol, A; Lichtman, A H; Finberg, R W et al. (2000) Cutting edge: heat shock protein (HSP) 60 activates the innate immune response: CD14 is an essential receptor for HSP60 activation of mononuclear cells. J Immunol 164:13-7
Kurt-Jones, E A; Popova, L; Kwinn, L et al. (2000) Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol 1:398-401
Bergelson, J M; Cunningham, J A; Droguett, G et al. (1997) Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275:1320-3
Solomon, K R; Rudd, C E; Finberg, R W (1996) The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes. Proc Natl Acad Sci U S A 93:6053-8
Bergelson, J M; Mohanty, J G; Crowell, R L et al. (1995) Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55). J Virol 69:1903-6
King, S L; Cunningham, J A; Finberg, R W et al. (1995) Echovirus 1 interaction with the isolated VLA-2 I domain. J Virol 69:3237-9
Bergelson, J M; Chan, M; Solomon, K R et al. (1994) Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses. Proc Natl Acad Sci U S A 91:6245-8
Kawaguchi, S; Bergelson, J M; Finberg, R W et al. (1994) Integrin alpha 2 cytoplasmic domain deletion effects: loss of adhesive activity parallels ligand-independent recruitment into focal adhesions. Mol Biol Cell 5:977-88
Bergelson, J M; St John, N F; Kawaguchi, S et al. (1994) The I domain is essential for echovirus 1 interaction with VLA-2. Cell Adhes Commun 2:455-64

Showing the most recent 10 out of 13 publications