Usage of KSHV gH/gL as a target for neutralizing antibodies and analysis of Eph-receptor interactions of KSHV and MHV-68 gH/gL
The human Herpesvirus (HHV-8), commonly referred as Kaposi’s Sarcoma-associated Herpesvirus (KSHV) is a member of the gammaherpesvirinae subfamily and a less well-known relative of the Epstein-Barr-Virus (EBV). KSHV is the causative agent for diseases like the Kaposi sarcoma (KS) as well as B cell malignancies such as primary effusion lymphoma (PEL) and multicentric Castleman’s disease. Primary infection of KSHV in healthy individuals is often asymptomatic, however individuals with a compromised immune system are at risk of developing KS lesions. Even though the prevalence of KS is considered relatively low in most parts of the world, it also is one of the most common cancers in HIV-sufferers and sub-Saharan African men. Currently, no therapy is capable of eliminating the latent KSHV infection and therefore only chemotherapy regimens and symptomatic therapy is possible, so far.
Several surface proteins are involved in the entry of KSHV into the host cells. Among them are the glycoprotein K8.1 (gK8.1) and the heterodimer gH/gL. GK8.1 is known for its function in surface attachment of the virion, while gH/gL is involved in the endocytic steps. We aim to use the KSHV gH/gL as an effective target for vaccine development, by obtaining neutralising antibodies from immunised mice or by selection of antigen specific B cells from patients in KS remission.
KSHV exhibits species specificity, limiting in vivo vaccine evaluation. Testing vaccine efficacy in a mouse model is a crucial step in developing a succeeding vaccine. To overcome this barrier, we will additionally investigate the closely related murine gammaherpesvirus 68 (MHV-68). By identifying the cellular receptors of MHV-68 gH/gL and assessing the ability of blockage in infection assays, we aim to establish MHV-68 as a functional surrogate model KSHV.
