Helmholtz Centre for Infection Research, Braunschweig, Germany
Student: Ana Cristina González Pérez, Ph.D. fellow
Supervisor: Prof. Dr. rer. nat. Melanie Brinkmann
Pathogens infiltrate our bodies daily but do not remain undetected. It is our immune system which recognizes these invaders and takes appropriate measures against them.
The immune system has several components. One of them, the type interferon (IFN) response, mediated by receptors called pattern recognition receptors (PRR), plays a key role to fight viral infection. Upon detecting nucleic acids of cellular or viral origin at aberrant locations, these receptors induce the secretion of cytokines called type I IFNs. These cytokines then bind to the type I IFN receptor (IFNAR), which is located on the plasma membrane. This leads to the generation of so called interferon stimulated gene products (ISGs). ISGs can directly inhibit viral replication, for example by shutting off protein synthesis. As a consequence, viruses have developed strategies to block the IFN response and/or ISG functions, or even use these antiviral defence systems for their own benefit. One family of viruses is especially well known for hijacking the immune system: the herpesviridae. Herpesviruses have a large DNA genome that encodes multiple proteins. A large portion of these proteins is dedicated to the modulation of the host immune response, allowing the establishment of lifelong latency.
Human cytomegalovirus (HCMV) is a herpesvirus that affects both immunocompetent and immunosuppressed individuals. In healthy individuals, HCMV usually causes only mild disease. However, in immunosuppressed individuals such as AIDS or transplant patients, HCMV infection can cause severe complications such as mononucleosis-like syndrome, encephalitis, retinitis, pneumonia, hepatitis and gastroenteritis. Another risk group are unborn children: HCMV infection during pregnancy can be transmitted from mother to child and can cause severe long-term sequelae such as hearing loss, microcephaly, intellectual deficits or vision abnormalities. In fact, HCMV is the most common non-genetic cause of hearing loss in children worldwide.
Via multiple PRR, HCMV infection potently induces secretion of type I IFNs, which then induce expression of a specific set of ISGs via the IFNAR. However, (i) how these ISGs affect HCMV replication, (ii) if HCMV developed countermeasures against certain ISGs or (iii) even uses them for its own benefit is poorly understood.
Our project aims to characterize the antiviral or proviral role of selected ISGs induced upon HCMV infection and to demonstrate their mechanism of action in the context of viral infection.
Melanie M. Brinkmann, Professor
Viral Immune Modulation Research Group
Helmholtz Centre for Infection Research