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Host genetic risk factors to viral diseases - a double-edged sword : Studies of norovirus and tick-borne encephalitis virus
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- Kindberg, Elin, 1981- (author)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- Svensson, Lennart, Professor (thesis advisor)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- Hinkula, Jorma, Professor (thesis advisor)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- ISBN 9789173933933
- Linköping : Linköping University Electronic Press, 2010
- English 77 s.
- Series: Linköping University Medical Dissertations, 0345-0082 ; 1183
- Doctoral thesis (other academic/artistic)
Abstract
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- It is today well known that the outcome of a certain infection depends on factors of both the host and the pathogen. Studies of host genetic susceptibility to infectious diseases aim to increase the understanding of why some individuals are more susceptible than others, to a certain infection. Knowledge of genetic susceptibility to a viral disease may be used in development of new therapeutic means, and also to recognize individuals who are at increased risk of severe symptoms if infected with a pathogen. It seems however that a risk factor for one disease may play a protective role in another situation; like a double-edged sword.In this thesis I have studied genetic factors affecting susceptibility to norovirus (NoV) and factors affecting the risk of developing tick-borne encephalitis (TBE) after infection with TBE virus (TBEV). NoV is the cause of the “winter vomiting disease”, affecting millions of people every year, and causing up to 200,000 fatalities among children in developing countries, each year. It is today recognized that the secretor status of an individual, i.e. the ability to express ABO blood groups and related antigens, in secretions and on mucosa, affect the risk of being infected by NoV. By studying authentic NoV outbreaks in Denmark, Spain and Sweden and by comparing the secretor status of affected and unaffected individuals we were able to confirm that secretor status have indeed great impact on susceptibility to some NoV strains, but also that there are strains circulating, which infect individuals regardless of secretor status.TBEV is endemic in many parts of Europe and Asia but studies have shown that 70-95% of all infections are asymptomatic or sub-clinical. Some individuals do however develop TBE, a severe disease including meningitis or encephalitis with or without myelitis. Also, many patients suffer from long-time sequelae and TBEV infections may in worst case be fatal. The reason for difference in disease outcome is not known and we have chosen to study if genetic factors affecting the immune response may play a role in disease outcome. To do this we used a prospectively collected Lithuanian material with samples from patients with TBE, AME (aseptic meningoencephalitis) and matched healthy controls. So far we have found that a deletion in chemokine receptor 5 (CCR5), a gene encoding a receptor involved in cell migration, is a risk factor for developing disease. We have also data showing that toll-like receptor 3 (TLR3), a receptor recognizing double stranded RNA (dsRNA), which is a product of TBEV replication, may instead of being protective increase the risk of TBE.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- Virology
- Virologi
Publication and Content Type
- vet (subject category)
- dok (subject category)
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