Kaposi’s sarcoma-associated herpesvirus (KSHV) was identified in 1994 and is one of the nine human herpesviruses known to date. Since its discovery, KSHV has been identified as the causative agent of three neoplasms, including (1) Kaposi’s sarcoma, a cancer of the blood vessels, 2) body cavity-based lymphoma, a cancer of white blood cells, and (3) Castleman’s disease, which causes severe lymph node enlargement.
Moritz Kaposi, a Hungarian doctor, first described Kaposi’s sarcoma in the 19th century. However, it was only with the identification of KSHV genetic material in Kaposi’s sarcoma, more than one hundred years later, that the US scientists Yuan Chang and Patrick Moore could show that a novel herpesvirus was the causative agent of this form of cancer.
A characteristic feature of all herpesviral infections is that healthy individuals can become infected, but in most cases they are able to control viral replication. The host and virus are thus able to peacefully coexist until the balance is disrupted, often due to a weakened immune system. For example, Kaposi’s sarcoma is a frequent complication in AIDS patients, as infection with human immunodeficiency virus (HIV) severely weakens the immune system. The weakened immune system is no longer able to control KSHV replication. Similarly, organ transplant recipients are frequently unable to control herpesviral replication due to immunosuppressive drugs that likewise inhibit the immune response.
The research groups of Melanie Brinkmann and Stephan Halle will jointly clarify the mechanisms through which KSHV and its homolog murine herpesvirus 68 (MHV68) are first recognized by the immune system and subsequently controlled by the immune system as the infection progresses. They will use two-photon microscopy to directly visualize the interplay between MHV68-infected cells and immune cells. It will thus be possible to determine the factors that are important for viral control on the single cell level.
Additionally, studying KSHV may give novel insights into vital cellular processes. Due to many millions of years of co-evolution, herpesviruses have learned key features of our immune defenses and even use some for their own benefit. How KSHV switches the immune response to favor establishment of its infection is not well understood but an important question. Analysis of its host manipulation will allow new insights into the interplay between KSHV and the host, as well as clarification of how KSHV contributes to cancer development.