New Herpesvirus Receptor Discovered That Allows Entry of Both Herpes Simplex-1And -2 And Animal Herpesviruses Into Human Cells

June 04, 1998

CHICAGO --- A new protein has been discovered that provides a pathway for several different types of herpesvirus, including two herpes simplex viruses (HSV), to infect human cells.

This protein, called a herpesvirus entry mediator, is the third receptor for HSV to be identified by the research team of microbiologist Patricia G. Spear of Northwestern University Medical School. Spear is the Guy and Anne Youmans Professor and chair of microbiology/immunology at the Medical School.

Herpes simplex virus is highly prevalent in humans, in part because it can establish latent infections in nerve cells and persist indefinitely with periodic reactivation of the virus. Consequences of viral replication include cold sores and fever blisters, similar lesions on the genitalia, corneal destruction, encephalitis and severe disease in newborns. The virus can bind to many types of human cells but is capable of penetrating only certain cell types.

Robert J. Geraghty, Spear and collaborators from the University of Pennsylvania, Philadelphia, described the new herpesvirus receptor in an article in the June 5 issue of the journal Science. Geraghty is a research associate in microbiology/immunology working with Spear at Northwestern.

They found that the protein, called HveC, is actually a co-receptor that could allow both HSV-1 and -2 to enter skin cells at the site of infection and to spread into cells of the nervous system.

In addition to serving as a co-receptor for HSV-1 and -2, this new receptor permits entry of other closely related forms of herpesvirus, porcine pseudorabies virus and bovine herpesvirus, into cells.

HveC has the broadest activity of the three herpesvirus co-receptors identified to date, both in terms of distribution of the receptor in human tissues and in the numbers of different herpesviruses and strains that can use the receptor for infection, Spear said.

The previously identified receptor, HveA, is limited in distribution principally to lymphoid tissues, and it does not permit entry of animal herpesviruses. HveB has a tissue distribution more like that of HveC but does not mediate entry of most HSV-1 strains.

Interestingly, HveB and HveC are closely related to the poliovirus receptor, which itself does not mediate entry of HSV-1 or -2 but does allow entry of the porcine and bovine herpesviruses mentioned here.

"Our results implicate HveC as the prime receptor for allowing HSV-1 and HSV-2 infection of mucosal surfaces and spread to the nervous system. It is a prime target for novel prophylactic or therapeutic interventions," Spear said.

Ongoing research in Spear's laboratory is directed toward identifying cell surface proteins that can mediate entry of herpes simplex virus into various cell types, including nerve cells, and defining the relevant mechanisms of entry into different human cells.

In addition to Geraghty, Spear's co-authors on this article were Claude Krummenacher and Gary H. Cohen, School of Dental Medicine and Center for Oral Health Research, University of Pennsylvania, Philadelphia; and Roselyn J. Eisenberg, Center for Oral Health Research and School of Veterinary Medicine, University of Pennsylvania, Philadelphia.

This work was supported by grants from the National Institute of Allergy and Infectious Diseases and the National Institute of Neurological Disorders and Stroke. Geraghty is supported by a National Research Service Award.
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Northwestern University

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