Herpes simplex virus 2 (HSV-2) is often a lifelong infection, flaring up to cause genital lesions and dying down again quickly. For healthy people, the body can usually fight off the flare-ups but these reactivation episodes are often frequent, and can sometimes persist at low levels for weeks in the genital skin. How the virus manages to successfully evade the host immune system in the genitals has remained unclear. Now VIDI scientists, including research scientist Dr. Tao Peng and co-director Dr. Larry Corey, have uncovered new information suggesting that HSV-2 blocks a specific type of immune signaling molecule as a means of evading detection by the immune system.
This type of signaling molecule, a cytokine called a type I interferon, is produced by cells of the innate immune system in response to invading pathogens. Peng and colleagues looked at genome-wide activation in herpes lesions cells, and found that while other interferon types were strongly induced during lesions, type I interferons were suspiciously absent.
The scientists then looked at fluorescently-stained cells in infected and uninfected genital skin, and found that innate immune cells known to secrete type I interferon (IFN-a and IFN-b), monocytes/macrophages, myeloid dendritic cells, and plasmacytoid dendritic cells, were present during lesions. Somehow, the virus prevents these cells from doing their job to secrete type I IFN, a potent antiviral cytokine. This may be a key means for HSV-2 to avoid detection and clearance by the body’s immune system.
EVASION OF MUCOSAL INNATE IMMUNE SYSTEM BY HSV-2. Peng T, Zhu J, Klock A, Phasouk K, Huang ML, Koelle DM, Wald A, Corey L. J Virol. 2009 Sep 30.