FP7Reintegration grant2013–2017

HSVMIR-IJ · Roles of miRNAs in Herpes simplex virus 1 infection

FP7 — People (Marie Curie Actions)

Duration
2013-10-01 → 2017-09-30
EU contribution
€100,000
Participants
1
Scheme
MC-CIG

Lines connect the coordinator with its partners.

Results in brief

Roles of miRNAs in Herpes simplex virus 1 infection

Project FP7-2013-PEOPLE-CIG #618587 “Roles of miRNAs in Herpes Simplex Virus 1 Infection and Pathogenesis (HSVmiR-IJ) led by dr. Igor Jurak at the Department of Biotechnology, University of Rijeka. Project Objectives. Herpes simplex virus is an important human pathogen and widely used model to study enveloped viruses and host defense mechanisms. The main focus of the research project was to investigate roles of miRNAs, regulatory small non-coding RNAs, in HSV-1 infection. It has been shown previously that HSV-1 encodes numerous miRNAs (Umbach et l. 2016, Jurak et al. 2010) and some of them are differentially expressed during productive and latent infection. The function of these molecules is poorly understood. With the help of Department and its administration, the project was successfully carried out and the research goals have been accomplished to an extent. The research project goals were 1) define the roles of HSV-1 encoded miRNA focusing on miR-H1/H6 and 2) define the roles of host miRNAs in virus replication. Due its complexity, the parts of project are still ongoing, however have been presented at research meetings and it is expected to be published within 2 years. IJ has defined the exact sequences of virus encoded miRNAs, which will greatly contribute to the future functional studies. Moreover, they have thoroughly explored the dynamic changes of host miRNAs during productive HSV-1, and found that only a subset of host miRNAs is dynamically changed, which might have significant effect on virus infection. Nonetheless, the main goal of the project has been fulfilled, i.e. I. Jurak has successfully integrated within the Department of Biotechnology and was offered the permanent position. Currently he acts as assistant professor at the department, the member of Committee for doctoral studies, and he is the head of the Laboratory for Molecular Virology. IJ has presented his research on several international conferences, published two publications, and has at least three manuscripts in writing. During the MC- grant he has recruited three doctoral students and one postdoc in his lab securing founds support them. IJ during the four year period has obtained the most competitive grant in Croatia (Croatina Research Foundation), a grant from the European Social Found and the support from University of Rijeka, which show, not only, the scientific activity of IJ but also his further development and the continuity. The foundation for a successful carrier was the MC grant, the support from the University (lab space and the equipment) and his limitless enthusiasm. IJs addition to the Department has bring an international expertise and research excellence, on which the Department and University builds its quality. Thus far, the laboratory has hosted more than 10 undergraduate students and enabled them to be involved in a competitive scientific work and trained for further academic career. Thus, taking together the MC grant has offered IJ development of his career, but also immensely contributed to our University.

Data: CORDIS, © European Union

Project objective

Herpes simplex virus 1 (HSV-1) is important human pathogen widely known as the causative agent of cold sores, and it is the leading infectious cause of blindness, and the most common cause of sporadic encephalitis. Although intensively studied, many fundamental aspects of the HSV-1 biology are poorly understood, including the control of latency and regulation of gene expression. We have recently discovered numerous miRNAs, a class of small regulatory non-coding RNAs, expressed by HSV-1 and closely related virus, HSV-2, revealing a new paradigm for the HSV gene regulation. Some of these miRNAs are conserved between these two viruses and expressed differentially during different phases of infection; however function of most HSV miRNAs is unknown. We hypothesize that miRNAs have a central role in modulating the host-pathogen interaction that leads to efficient virus replication and establishment of latency. Also, we hypothesize that miRNA have a central role in establishing the threshold for the reactivation upon different stimuli, i.e. control of the lytic-latent switch. Here we seek to understand the roles of microRNAs (miRNAs), encoded by the virus and host, in the regulation of gene expression during lytic and latent HSV-1 infection. We primarily focus on functions of miR-H1 and miR-H6, HSV-1 miRNAs abundantly expressed during lytic infection, and lytic and latent infection, respectively, and miRNAs almost entirely complementary to each other. In our preliminary data, we have generated the HSV-1 mutant impaired for the expression of these miRNAs and characterize the mutant in vitro and in a mouse model. In addition, to enable high-throughput technologies, we have tested several in vitro latency models and characterized the expression of HSV-1 and host miRNAs in these models. At the conclusions of these studies we will have better understanding of the HSV-1 biology including the virus pathogenesis, and it might lead to novel approaches to cure HSV infections.

Original text from CORDIS.

Participants

  • SVEUCILISTE U RIJECI · RijekaCoordinatorCroatia

Links

Data: CORDIS, © European Union