Viral Immune Modulation

Pathogens (germs) infiltrate our bodies daily but do not remain undetected. They encounter the strong defenses of our immune system, which recognizes invaders and promptly takes appropriate measures. However, many pathogens can produce life-long infections even with an intact immune system. The herpesvirus family is one such group of pathogens. Upon infection, herpesviruses establish a chronic infection and become lifelong companions. 

Leader

Our Research

Herpesviruses are extremely complex viruses. We are just beginning to understand exactly how these pathogens manipulate our immune system to establish chronic infections. In order to develop new therapies and vaccines, it is first necessary to understand the interplay between herpesviruses and their hosts. 

Figure 1. The herpesvirus life cycle: primary infection is followed by a phase of latency. When the delicate balance between the virus and immune system is disrupted, herpesviruses can reactivate from latency and enter the lytic phase, during which new virus particles are formed.

Research in the “Viral Immune Modulation” group focuses on how herpesviruses are recognized by the innate immune system. In addition, our research analyzes how these viruses so successfully establish chronic infections. The question of how herpesviruses circumvent or weaken the defensive line of our innate immune system plays a central role, as this is a requirement for the viruses to successfully establish lifelong infection

Figure 2. The innate immune system is the first line of defense against pathogens. Pattern recognition receptors recognize viruses immediately upon infection of host cells. The receptors then induce signaling cascades that result in the production of second messengers. These messengers are important for activation of the pathogen-specific adaptive immune response.

Fundamental research for development of novel therapies 

Via millions of years of coevolution, herpesviruses have adapted themselves perfectly to their hosts. They know exactly which switches to pull to weaken certain aspects of the immune response as well as to enhance responses that benefit them. The mechanisms used by herpesviruses to manipulate our immune system are explored in research projects in the “Viral Immune Modulation” group. One goal of the research group is to identify novel viral proteins that are directly involved in manipulation of immune defenses. These proteins are potential targets for the development of new antiviral therapies. 

Figure 3. Herpesviruses are complex viruses that have reserved a large portion of their genetic material for immune modulation genes. They have developed an impressive array of elegant mechanisms to establish life-long infections.

Spotlight: the herpesviruses CMV and KSHV 

Research in the “Viral Immune Modulation” group focuses on two members of the herpesvirus family: human herpesvirus 5, also known as cytomegalovirus (CMV), and human herpesvirus 8, or Kaposi’s sarcoma-associated herpesvirus (KSHV). 

CMV is a common pathogen, thought to infect half of the European population. In many healthy individuals, CMV infection is unrecognized - it may cause mild illness or even be completely asymptomatic. However, in patients with weakened immune systems, for example in HIV/AIDS patients and transplant recipients, CMV infection can cause severe complications. 

In addition, although it is not always common knowledge, CMV is the most common viral cause of birth defects. Infection of the mother during pregnancy can lead to infection of the fetus, resulting in permanent damage observed at birth or later in childhood. CMV-induced birth defects include mental handicap, deafness, microcephaly, and/or visual impairment.  In fact, CMV infection during pregnancy is the most common cause of non-genetic deafness in children. 

To date, there is no vaccine against CMV and there is only a limited selection of antiviral drugs available, which are unfortunately accompanied by serious side effects. 

KSHV was first discovered in 1994. Since then, it has been identified as the causative agent of at least three types of cancer

  1. a cancer of blood vessels, known as Kaposi’s sarcoma, 
  2. a type of lymphoma, or cancer of white blood cells, known as primary effusion lymphoma, 
  3. a form of lymph node enlargement, known as multicentric Castleman’s disease. 

The goal of our research activities is to gain novel insights into the interplay between the herpesviruses CMV and KSHV and their hosts, and thus better understand how these viruses cause illness. These insights are the foundation required to develop innovative, specific therapies against herpesviruses. 

Publications

Here you can find a complete list of publications.

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