uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Sensing Arboviruses : Dengue and Chikungunya virus
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
2017 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
Abstract [en]

Arboviruses are one of the key health concerns over the past 20 years. There were several outbreaks of arboviruses across the globe which brought attention to some forgotten pathogens. Dengue (DENV) and Chikungunya (CHIKV) viruses are considered re-emerging pathogens as these pathogens expand to new regions and caused large epidemics in South East Asian and Indian Ocean islands. The response of innate immune system towards these viruses are not fully understood especially virus sending by toll-like receptors (TLRs) and the effect of virus infection to innate immune cells such as monocytes.   

First project has been focused on the DENV interaction with TLRs to induce NF-κB activity. During this research project, we elucidated the mechanism of DENV sensing by TLR2. We demonstrated that DENV can activate NF-κB via TLR2 occurs in a replication independent manner. We also showed that as well TLR2 mediated activation is initiated already at the cell surface. Interestingly, while internalization of the TLR2 and/or the virus increases the level of NF-κB activation,   occurs irrespectively of the ability of the virus to fuse from within the endosomal compartment. DENV/TLR2 axis activates NF-κB in a serotype-independent manner, but the ability to activate NF-κB might not be shared between Flaviviruses.

Second project has been focused to determine the effect of CHIKV infection on PBMCs and monocyte in context of PBMCs. CHIKV infection increases human peripheral blood mononuclear cells (PBMCs) viability as well as cause the shift of monocyte subsets towards an intermediate phenotype and this effect in not comparable to stimulation with TLR2/4/7 agonists. The effect of CHIKV infection on PBMCs viability and monocyte subset distribution is abolished by pre-treatment of PBMCS with TLR4/7 agonists.  However, we were unable to quantify CHIKV infection in PBMCs.

In conclusion, we presented a novel role of TLR2 during early host cell interactions with DENV and presented elucidate how CHIKV shapes immune systems response. The obtained knowledge will contribute to the understanding the mechanism of virus induced immunopathology.

 

 

Place, publisher, year, edition, pages
2017. , 60 p.
Keyword [en]
Dengue, Chikungunya, virus, monocytes, TLR2
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-328634OAI: oai:DiVA.org:uu-328634DiVA: diva2:1136640
External cooperation
University Medical Center Groningen
Educational program
Master Programme in Biology
Supervisors
Examiners
Available from: 2017-09-05 Created: 2017-08-28 Last updated: 2017-09-05Bibliographically approved

Open Access in DiVA

fulltext(2593 kB)0 downloads
File information
File name FULLTEXT01.pdfFile size 2593 kBChecksum SHA-512
c63beb3a9020feb29c699cd17124fb38189ee0c05ea1a4584d25ed3c9d0c86fa3cea36f56936cc5e4da769a7e275a5254bf8ada820579428f68df38500e302ee
Type fulltextMimetype application/pdf

By organisation
Biology Education Centre
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

urn-nbn

Altmetric score

urn-nbn
Total: 537 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf