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Journal of Virology, June 2005, p. 7419-7430, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7419-7430.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A New Class of Receptor for Herpes Simplex Virus Has Heptad Repeat Motifs That Are Common to Membrane Fusion Proteins

Aleida Perez,1 Qing-Xue Li,1,{dagger} Pilar Perez-Romero,1 Gregory DeLassus,1 Santiago R. Lopez,1 Sarah Sutter,2 Ning McLaren,1 and A. Oveta Fuller1,2*

Department of Microbiology and Immunology,1 Program in Cellular and Molecular Biology, School of Medicine, University of Michigan, Ann Arbor, Michigan 48109-06202

Received 28 September 2004/ Accepted 14 February 2005

We isolated a human cDNA by expression cloning and characterized its gene product as a new human protein that enables entry and infection of herpes simplex virus (HSV). The gene, designated hfl-B5, encodes a type II cell surface membrane protein, B5, that is broadly expressed in human primary tissue and cell lines. It contains a high-scoring heptad repeat at the extracellular C terminus that is predicted to form an {alpha}-helix for coiled coils like those in cellular SNAREs or in some viral fusion proteins. A synthetic 30-mer peptide that has the same sequence as the heptad repeat {alpha}-helix blocks HSV infection of B5-expressing porcine cells and human HEp-2 cells. Transient expression of human B5 in HEp-2 cells results in increased polykarocyte formation even in the absence of viral proteins. The B5 protein fulfills all criteria as a receptor or coreceptor for HSV entry. Use by HSV of a human cellular receptor, such as B5, that contains putative membrane fusion domains provides an example where a pathogenic virus with broad tropism has usurped a widely expressed cellular protein to function in infection at events that lead to membrane fusion.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Michigan School of Medicine, 6736 Medical Sciences II, 0620, Ann Arbor, MI 48109-0620. Phone: (734) 647-3830. Fax: (734) 764-3562. E-mail: fullerao{at}umich.edu.

{dagger} Present address: NIAID, Bldg. 10, Rm. 11N214, Bethesda, MD 20892.

Journal of Virology, June 2005, p. 7419-7430, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7419-7430.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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