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Scientists discover mechanism of herpes virus cell entry machinery

March 11, 2017

There is no cure for herpes viruses. Upon infection, the viruses remain in the body for life and can stay inactive for long periods of time. When active, however, different herpes viruses can cause cold sores, blindness, encephalitis or cancers. More than half of Americans are infected with herpes simplex virus type 1, HSV-1, by the time they reach their 20s. About one in six Americans is infected with herpes simplex virus type 2, HSV-2, which is the virus responsible for genital herpes. Complications of HSV-2, a sexually-transmitted disease, include recurrent painful genital sores, psychological distress and, if transmitted from mother to child, potentially fatal infections in newborns.

Herpes viruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpes viruses inexplicably require two conserved fusion-machinery components, gB and the heterodimer gH-gL, plus other nonconserved components. gB is a class III viral fusogen, but, unlike other members of its class, it does not function alone.

"We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2," said Roselyn J. Eisenberg, professor of microbiology at the University of Pennsylvania School of Veterinary Medicine. "gH-gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen."

"We propose that gH-gL activates gB for fusion, possibly through direct binding," said Gary Cohen, professor of microbiology at the University of Pennsylvania School of Dental Medicine. "Formation of a gB-gH-gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB-gH-gL interface a promising antiviral target."

Source: University of Pennsylvania