A team of researchers from the Yeshiva University’s Albert Einstein College of Medicine, New York, and the Pontificia Universidad Católica de Chile, has proposed a new approach for preventing infections due to the highly common herpes simplex viruses, the microorganisms responsible for causing genital herpes and cold sores.
Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) are members of the herpes virus family Herpesviridae. They are known to infect skin cells as well as cells lining the cervix and the genital tract.
A study, published in the Journal of the American Medical Association in 2006, estimates that nearly 60 percent of U.S. men and women between the ages of 14 and 49 carry HSV-1.
According to a 2010 national health survey, about 16.2 percent of Americans between 14 and 49 are infected with HSV-2 – a lifelong and incurable infection that can cause recurrent and painful genital sores and can make those infected with the virus two-to-three times more likely to acquire HIV.
The team, led by Prof Betsy Herold of the Children’s Hospital at Montefiore, had previously shown that infection by the herpes viruses depends on calcium released within the cells.
They found that calcium release occurs because the viruses activate a critical cell-signaling molecule called Akt at the cell membrane.
As part of their investigation of Akt’s role in herpes infections, the scientists took laboratory cultures of those human cell types and mixed them for 15 min with four different drugs known to inhibit Akt. The cells were then exposed for one hour to HSV-2. All four drugs significantly inhibited herpes virus infection in each of the cell types. By contrast, cells not pretreated with the Akt inhibitors were readily infected on exposure to the virus.
“We’ve essentially identified the molecular ‘key’ that herpes viruses use to penetrate cell membranes and infect cells of the human body,” said Prof Herold, senior author of a paper published online in the Journal of the Federation of American Societies for Experimental Biology.
“For people infected with herpes, the drug acyclovir helps prevent herpes outbreaks from recurring and lowers the risk of transmitting the infection to others,” Prof Herold said.
“But some people have herpes infections that don’t respond to acyclovir, and unfortunately there is no effective vaccine. So new approaches for suppressing and treating herpes infections are badly needed, and our findings indicate that inhibiting Akt should be a useful therapeutic strategy to pursue.”
Bibliographic information: Natalia Cheshenko et al. HSV activates Akt to trigger calcium release and promote viral entry: novel candidate target for treatment and suppression. The FASEB Journal, published online before print March 18, 2013; doi: 10.1096/fj.12-220285