Vaccine and Infectious Disease Division

The immune system’s diverse response to HSV-2

While antiviral drugs exist to treat the symptoms caused by herpes simplex virus 2 (HSV-2), the drugs have no effect on the disease’s spread and no effective vaccine has been developed.  HSV-2 is one of the most common STDs worldwide, and while alone its effects are often not severe, it greatly increases the risk of HIV acquisition.  The body’s immune response to the virus is not well understood, but it is known that when the virus reactivates in the genitals, a type of immune cell called cytotoxic T cells cluster to the area of viral resurgence.   Since these T cells change their molecular characteristics based on the pathogen they encounter, and stimulating such cells may be an important step in developing an effective HSV-2 vaccine, it is important to understand the nature of these clustering cells in HSV-2 reactivation episodes.

To that end, VIDD staff scientist Dr. Kerry Laing and her colleagues, including VIDD joint assistant member Dr. Amalia Magaret and co-director Dr. Larry Corey, characterized cytotoxic T cells in the blood of 55 people infected with HSV-2.  The researchers looked at which specific HSV-2 proteins were targeted by cytotoxic T cells, and found that proteins expressed early in cellular infection were targeted at a higher rate than proteins expressed later.  Within those proteins, a variety of segments, or epitopes, were specifically targeted by the T cells; in addition to previously known epitopes, Laing and colleagues also found several previously unidentified epitopes.  Besides the T cells’ targets, the researchers also looked at their function.  In some chronic viral infections, cytotoxic T cells eventually become exhausted and lose the ability to perform their normal tasks, such as dividing and producing cytokines, small signaling proteins.  However, the HSV-2-specific cytotoxic T cells retained this functionality in many individuals.  The diversity observed in these cells’ targets and function may provide a portal to elucidate which T cell responses are most important for containment of the disease.

Laing KJ, Magaret AS, Mueller DE, Zhao L, Johnston C, De Rosa SC, Koelle DM, Wald A, Corey L.  Diversity in CD8(+) T Cell Function and Epitope Breadth Among Persons with Genital Herpes.  J Clin Immunol. 2010 Sep;30(5):703-22.