Susceptibility to infection: What part do genes play?

What role does the human genome play in susceptibility to infection? How do genes influence the multiplication of viruses and our defences against them? The RESIST team is tackling these questions – so that we can better predict how severe an infection is likely to be for a given individual and thus reach conclusions on the best treatment for him or her. Furthermore, people who are especially at risk for infection can be protected at an early stage – by vaccination, for example.

This can be crucial for furvival of some individuals infected by the cold virus RSV. For example, RSV can cause severe to life-threatening respiratory infections in young children.

Varicella zoster and herpes simplex viruses may also cause serious diseases, such as shingles or encephalitis.

RESIST will also explore the genetic causes of severe congenital immune deficiencies. In many cases, it remains unclear which genetic defects cause these deficiencies and why the immune system does not respond effectively. Bacteria and fungi are for example able to cause severe infection in people with a genetically determined susceptibility to infection.

Projects in Area A (genes)

A1

Which genetic factors make some children particularly susceptible to severe RSV infections?

The Respiratory Syncytial Virus (RSV) is a globally distributed respiratory pathogen. In the winter season it causes epidemic respiratory infections in all age groups. Among healthy adults, RSV infections are generally mild with common cold-like symptoms. However, primary RSV infections among infants can take a severe course…

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A2

Congenital immunodeficiency – How can the diagnosis be improved so that an early identification of as many affected persons as possible can be achieved?

The fitness of the immune system is unevenly distributed in the population. On the one hand there are anecdotal reports on the “90-yr-old smoker, who has never been admitted to hospital”; on the other hand there are immunocompromised individuals who would not survive without medical intervention, sometimes necessitating even bone marrow transplantation…

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A3

Varizella Zoster Virus – which genetic factors lead to severe disease progressions? How does the virus manage to persist in the body permanently and what causes reactivation?

Varicella zoster virus (VZV) infects the majority of people in industrialised countries. VZV establishes latency in neurons, remaining lifelong in the infected individual. Reactivation of VZV normally results in shingles, characterized by a painful rash…

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A4

Herpes and atopic dermatitis: Which mechanisms lead to severe disease progression after herpes infections in humans with atopic dermatitis?

The human alpha herpesviruses herpes simplex virus type 1 (HSV-1), HSV-2 and Varicella Zoster Virus (VZV) cause diseases ranging from painful and stigmatizing facial, oral and genital lesions to life-threating encephalitis, Meningitis…

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A5

What genetic changes predispose people to infections?

We aim to understand why the immune system of some individuals is unable to fight infections or control inflammation as the one of most of the people does. We are in particular interest in understanding how genetic could explain this variability…

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A6

Is the human virome a potential factor of infection susceptibility?

We study the genetic diversity of the virosphere at different scales because we are interested in better understanding the diversity of viruses both across eukaryotes and within the human virome…

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