ESR13 - Identification of novel immune modulatory mechanisms of human cytomegalovirus

Helmholtz Centre for Infection Research, Braunschweig, Germany

 

Student: Markus Fabits, Ph.D. fellow

Supervisor: Prof. Dr. rer. nat. Melanie Brinkmann

 

 

 

 

Human cytomegalovirus (hCMV) is a common virus that is spread worldwide in the human population. After primary infection, which often occurs without any symptoms, hCMV stays in the body for life in a dormant state and can reactivate under certain circumstances. In people with an intact immune system, hCMV infection is usually well controlled and the human body is protected from illness. However, if the immune system is not working properly, e.g. in immunocompromised organ transplant patients, HIV-infected people or people with genetic deficits, hCMV can cause severe diseases. Moreover, babies that were infected with hCMV by their mother during pregnancy can develop severe complications that are either apparent directly after birth or develop at later stages. Health problems due to congenital CMV infection include organ malformations, vision and hearing loss and developmental delay.

 

 

 

Important sentinels of our immune system are proteins that detect intruders and initiate a potent defense program against them. These proteins are called pattern recognition receptors (PRR) and are present in almost every cell in our body. PRR guard the cell surface and the interior of the cell and recognize either unique patterns of pathogens or perturbations that are induced by the infection. The invaded body cells then secrete signal molecules, called interferons, which further fight the intruders by creating an antiviral state and additionally warn surrounding uninfected cells about an ongoing infection. This first line of defense is deployed by the so-called innate immune system (Figure).

 

 

 

However, hCMV evolved elegant and efficient countermeasures to overcome immune control and ensure lifelong persistence. The aim of this project is to first identify individual hCMV proteins that counteract the early innate immune response mediated by PRR (Figure B). As a second step, we will analyse the role of the identified protein in the context of virus infection. To do so, we will create a mutant virus that lacks the identified PRR modulator and analyse its effect on the IFN response in comparison to wild type hCMV.

 

 

 

With the help of molecular, cell biological and immunological tools we will then study how the identified viral IFN modulator exerts its function. An increasing knowledge of hCMV immune evasion strategies may lead to improved treatment options to prevent infection and subsequent lifelong persistence of hCMV.

 

 

 

 


 

Contact details

Melanie M. Brinkmann, Professor

Viral Immune Modulation Research Group

Helmholtz Centre for Infection Research

Inhoffenstrasse 7

38124 Braunschweig

Germany