A new class of receptor for herpes simplex virus has heptad repeat motifs that are common to membrane fusion proteins.
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.
Perez
Aleida
A
Department of Microbiology and Immunology, University of Michigan School of Medicine, 6736 Medical Sciences II, 0620, Ann Arbor, MI 48109-0620, USA.
Li
Qing-Xue
QX
Perez-Romero
Pilar
P
Delassus
Gregory
G
Lopez
Santiago R
SR
Sutter
Sarah
S
McLaren
Ning
N
Fuller
A Oveta
AO
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D008565:Membrane Proteins; D011991:Receptors, Virus