Innate immunity to hantaviruses

HANTA-INNATE

LOGO

The logo is an schematic representation of the hantavirus, with the three viral RNA genome particles as squares, that as well represent the Croatian Grb`s squares and colours. The circle represents the viral coat, and by being interrupted by the project name on the right side creates the effect of a capital C, from Croatia. 

SUMMARY OF THE PROJECT

Hantaviruses, belonging to the family Bunyaviridae, are enveloped RNA viruses, which cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia (up to 20% mortality rate), and hantavirus cardiopulmonary syndrome (HPS) in Americas (up to 40% mortality rate). A broad spectrum of HFRS clinical conditions has been recognized, ranging from unapparent or mild to a fulminant hemorrhagic process with severe renal failure and death.
In Europe there are two main HTV which cause HFRS: Puumala (PUUV) and Dobrava (DOBV), while almost whole Croatia is endemic for HTV (except the coastal region), with predomination of PUUV circulation.
The reservoirs for HTV are small rodents with persistent infection and no manifestation of disease. The infection in humans is a consequence to the exposure to aerosols originated in saliva, urine, or faeces of rodents, while one of the most effective preventive methods is the control of animal populations in residential areas.
There is still a significant lack of knowledge about the immune response to HTV. A strong proinflammatory response during acute infection in humans, is probably responsible for viral clearance but also for potentially fatal proinflammatory-mediated disease. In the south-east Europe both DOBV and PUUV virus co-circulate, although these two viruses are more distantly related and cross-protection might not be seen. The lack of an animal model additionally hinders HFRS research. So far, no effective antivirals, vaccines, or immunotherapeutics exist for HFRS.

Goal
The overall objective of this project is to identify some key elements of innate immune response to HTV, their crosstalk, and potential mediation by regulating agents.

Specific Aims
1) To determine the key mechanisms which contribute to the interaction of innate immune players during acute HTV infection.
2) To explore possible regulating pathways of the innate immune response during HTV infection.

Impact and outcomes
As mentioned above, there is a lack of knowledge in the mechanism of immune response to HTV, and no effective antivirals, vaccines, or immunotherapeutics exist for HFRS. Therefore, our study is an unique opportunity in which we plan to detect and compare elements of innate immunity and possible immunosuppressive response in acute HFRS infection, and in experimentally simulated infections. The proposed research will contribute to substantial new knowledge on innate immune response to HTV, and aid to the future potential development of effective treatments for HFRS.

PROJECT DURATION
The project started on 01.07.2014, and will be completed on 30.06.2018.

FUNDING
HRZZ - Croatian Science Foundation  
The total budget of the project has been funded by the Croatian Science Foundation for four years with a total amount of 992,495.00 HRK (over 130,000 €). 

PROJECT TEAM MEMBERS 
University Hospital for Infectious Diseases, Zagreb  
Prof. Alemka Markotić, MD, PhD (Principal Investigator) Curriculum Vitae.pdf
Oktavija Đaković Rode, MD, PhD (Researcher) Curriculum Vitae.pdf
Lidija Cvetko Krajinović, PhD (postdoctoral fellow)  Curriculum Vitae.pdf
Ivan-Christian Kurolt, PhD (postdoctoral fellow) Curriculum Vitae.pdf
Petra Svoboda, BSc (PhD student)  Curriculum Vitae.pdf
Željka Mačak Šafranko, PhD (postodoctoral fellow) Curriculum Vitae.pdf
Branka Žibrat, BSc (technician)

Hebrew University Faculty of Medicine, Jerusalem, Israel
Professor Ofer Mandelboim, PhD Curriculum Vitae.pdf

Medical Faculty, University of Rijeka
Đurđica Cekinović, MD, PhD Curriculum Vitae.pdf

Medical Faculty, University of Split
Ass. Prof. Dragan Ledina, MD, PhD Curriculum Vitae.pdf

Croatian Institute for Public Health, Zagreb
Ljiljana Žmak, MD, PhD Curriculum Vitae.pdf

GROUP PICTURE...soon to come



COLLABORATIONS



IN THE NEWS


Lidija Cvetko Krajinović and Alemka Markotić visited professor`s Mandelboim Laboratory at the The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, The Hebrew University, Jerusalem, Israel and proceeded with research on NK cells and hantaviruses.

(The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, The Hebrew University, Jerusalem, Israel)


- A new Postdoctoral Fellow (Juan Jose Gonzalez Plaza) joined our team in June 2015.
 
- In 2015 the Hanta-Innate research team became a part of the Center of Excellence for Virus Immunology and Vaccines under the coordination of Prof Stipan Jonjić.


- Postodoctoral Fellow (Juan Jose Gonzalez Plaza) left our team at the end of March 2016.


- Finally, after three long years we're off for our long trip to the Xth International Conference on HFRS, HPS & Hantaviruses organized in Fort Collins, Colorado, USA to present some of our data. This is the biggest scientific meeting for researches in the field of Hantaviruses and the diseases they cause which is held every three years. 


- Two of our team members, Lidija Cvetko Krajinović, PhD and Ivan-Christian Kurolt, PhD, have been awarded a travel grant of $1000 each by the International Society for Hantaviruses (HFRS and HPS) to present their results at the Xth International Conference on HFRS, HPS & Hantaviruses. The picture below shows them with the other awardees in the beautiful Organ Recital Hall (ORC) at the University Center for the Arts at Colorado State University.



- We welcome our new Postdoctoral Fellow (Željka Mačak Šafranko) who joined our team in July 2016.


Talks
-Lidija Cvetko Krajinović, Heidi Spratt, Ante Tadin, Antea Topić, Rok Čivljak, Allan R. Brasier, Slobodan Paessler, Alemka Markotić: Early slowdown of the peripheral immune response triggered by Puumala virus infection. X International Conference on HFRS, HPS & Hantaviruses, Fort Collins, Colorado, USA, May 31st to June 3rd, 2016. (oral presentation)
- Ivan-Christian Kurolt, Lidija Cvetko Krajinović, Alemka Markotić: Micro RNAs in urine as potential biomarkers for severitys of hemorrhagic fever with renal syndrome. X International Conference on HFRS, HPS & Hantaviruses, Fort Collins, Colorado, USA, May 31st to June 3rd, 2016. (oral presentation)
 

Posters
- Lidija Cvetko Krajinović, Heidi Spratt, Ante Tadin, Antea Topić, Rok Čivljak, Allan R. Brasier, Slobodan Paessler, Alemka Markotić: [Unspecific and specific immunity to hantaviruses].  82nd Scientific-Professional Symposium with international participation – Zoonoses, Slavonski Brod, Croatia, 28.–30.05.2015. (poster presentation)
- Petra Svoboda, Lidija Cvetko Krajinović, Petra Čikeš, Antea Topić, Martina Bosnar, Vesna Eraković Haber, Davor Jugović, Alemka Markotić: Cytokine and chemokine kinetics and their potential as biomarkers in patients with Puumala virus infection. X International Conference on HFRS, HPS & Hantaviruses, Fort Collins, Colorado, USA, May 31st to June 3rd, 2016. (poster presentation)

CONTACT
Prof. Alemka Markotić, MD, PhD
Head of the Research Department, University Hospital for Infectious Diseases "Dr. Fran Mihaljević"
Mirogojska 8, 10 000 
Zagreb, Croatia
Tel/fax: 385-1-2826-148
Mobile phone: 385-(0)91-4012 648
E-mail: res.dept.bfm@gmail.com