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New Approach for Stopping Herpes Infections

Researchers target Akt cell-membrane molecule (Mar. 25)

Researchers at Albert Einstein College of Medicine of Yeshiva University have developed a new strategy for preventing infections due to herpes simplex viruses, the microbes responsible for causing genital herpes (herpes simplex virus 2) and cold sores (herpes simplex virus 1). The findings, published online in the FASEB Journal, could lead to new drugs for treating or suppressing herpes virus infections, according to the investigators.

“We’ve essentially identified the molecular ‘key’ that herpes viruses use to penetrate cell membranes and infect cells of the human body,” said co-author Betsy Herold, MD.

Herpes viruses are known to infect skin cells as well as cells lining the cervix and the genital tract. A 2006 study published in JAMA estimated that nearly 60% of U.S. men and women between the ages of 14 and 49 years carry the HSV-1 virus. In addition, the CDC estimates that about 1 in 6 Americans (16.2%) between the ages 14 and 49 years are infected with herpes simplex virus type 2 (HSV-2), according to a 2010 national health survey. Infection with HSV-2 can cause recurrent, incurable genital sores. Moreover, people infected with HIV-2 are two to three times more likely to acquire the human immunodeficiency virus (HIV).

Herold and her colleagues had previously shown that infection by the herpes viruses depends on calcium released within cells. In the new study, 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 researchers took laboratory cultures of those human cell types and mixed them for 15 minutes with four different drugs known to inhibit Akt. The cells were then exposed for 1 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.

“For people infected with herpes, the drug acyclovir helps prevent herpes outbreaks from recurring and lowers the risk of transmitting the infection to others,” 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.”

Source: Albert Einstein College of Medicine; March 25, 2013.

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