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Biochemical and functional analysis of smallpox growth factor (SPGF) and anti-SPGF monoclonal antibodies

Kim, Mikyung and Yang, Hailin and Kim, Sung-Kwon and Reche, Pedro A and Tirabassi, Rebecca S and Hussey, Rebecca E and Chishti, Yasmin and Rheinwald, James G and Morehead, Tiara J and Zech, Tobias and Damon, Inger K and Welsh, Raymond M and Reinherz, Ellis L (2004) Biochemical and functional analysis of smallpox growth factor (SPGF) and anti-SPGF monoclonal antibodies. The Journal of Biological Chemistry, 279 (24). pp. 25838-48. ISSN 0021-9258

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Abstract

Variola, the causative agent of smallpox, is a highly infectious double-stranded DNA virus of the orthopox genus that replicates within the cytoplasm of infected cells. For unknown reasons prominent skin manifestations, including "pox," mark the course of this systemic human disease. Here we characterized smallpox growth factor (SPGF), a protein containing an epidermal growth factor (EGF)-like domain that is conserved among orthopox viral genomes, and investigated its possible mechanistic link. We show that after recombinant expression, refolding, and purification, the EGF domain of SPGF binds exclusively to the broadly expressed cellular receptor, erb-B1 (EGF receptor), with subnanomolar affinity, stimulating the growth of primary human keratinocytes and fibroblasts. High affinity monoclonal antibodies specific for SPGF reveal in vivo immunoprotection in a murine vaccinia pneumonia model by a mechanism distinct from viral neutralization. These findings suggest that blockade of pathogenic factor actions, in general, may be advantageous to the infected host.


Item Type:Article
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Molecular biology
Sciences > Computer science > Bioinformatics
ID Code:9336
Deposited On:06 Aug 2009 10:15
Last Modified:06 Feb 2014 08:23

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