The human pathogen Kaposi’s sarcoma-associated herpesvirus (KSHV) and the related rhesus monkey rhadinovirus (RRV)
We are studying the human pathogen Kaposi’s sarcoma-associated herpesvirus (KSHV), a gamma2-herpesvirus or rhadinovirus, and the related rhesus monkey rhadinovirus (RRV), a similar virus of rhesus macaques. KSHV is a tumor virus. It is associated with Kaposi’s sarcoma and two B cell malignancies, primary effusion lymphoma and multicentric Castleman’s disease. KSHV causes significant morbidity and mortality in Sub-Saharan Africa and in the context of HIV infection.
Virus-receptor interactions
A major focus of our research is on the interaction of viral glycoproteins with cellular receptors. These receptor interactions are critical for entry of the virus into host cells and constitute a major determinant of viral tropism, governing which cell types and which tissues are targeted by the virus. We are using our knowledge about specific virus-receptor interactions to generate modified viruses that are defective in the use of certain receptors or that exhibit altered cell and tissue tropism. In the long run we want to apply these modified viruses as experimental vaccines and vaccine vectors.
Receptor function
A second focus is on the function of the cellular receptors themselves. The cellular receptor for the KSHV gH/gL glycoprotein complex, EphA2, and related Eph family receptors are used by several viral and by at least one bacterial pathogen. Recently, it was discovered that even malaria parasites bind this receptor. In our opinion, this kind of convergent evolution warrants a closer examination of EphA2 and of similar receptors to clarify why such a diverse set of pathogens interacts with the same type of protein.
Transmission, epidemiology, and disease
Finally, our group is interested in the biology of the gamma2-herpesviruses in a more general way. The DPZ colony is a unique resource for the collection of virus isolates, not only from rhesus macaques. Sequencing of virus isolates will allow us to analyze the diversity of these viruses and to identify the routes of transmission within the colony. Collaborative studies with the veterinary pathology unit may allow us to discover associations with disease.
Selected Publications
- Liu S, Schlagowski S, Großkopf AK, Khizanishvili N, Yang X, Wong S, Guzmán E, Backovic M, Scribano S, Cordsmeier A, Ensser A, Hahn AS
Kaposi’s sarcoma-associated herpesvirus (KSHV) gB dictates a low-pH endocytotic entry pathway as revealed by a dual-fluorescent virus system and a rhesus monkey rhadinovirus expressing KSHV gB.
(Kopie 1)PLoS Pathogens, accepted - Liu S, Großkopf AK , Yang X, Mannheim ME, Backovic M, Scribano S, Schlagowski S, Ensser A, Hahn AS
Kaposi's sarcoma-associated herpesvirus glycoprotein K8.1 is critical for infection in a cell-specific manner and functions at the attachment step on keratinocytes.
(Kopie 1)J Virol. 2023 Oct 31;97(10):e0083223. - DOI - - Fricke T, Großkopf AK, Ensser A, Backovic M, Hahn AS
Antibodies Targeting KSHV gH/gL Reveal Distinct Neutralization Mechanisms
(Kopie 1)Viruses, 2022, 14 (3), 541