Community Research and Development Information Service - CORDIS

Periodic Report Summary 1 - INMA (Immune and Neuromodulation Mediated by Alphaherpesviruses)

1. Summary (max. 500 words):
The three human alphaherpesviruses, herpes simplex virus type 1, type 2 (HSV-1 and HSV-2, respectively) and varicella zoster virus (VZV), are highly prevalent pathogens that establish latency in neurons of the peripheral nervous system. HSV-1 and HSV-2 cause a variety of diseases such as cold sores, genital herpes and encephalitis. Primary infection with VZV causes varicella, whereas reactivation causes zoster that may lead to post-herpetic neuralgia (PHN), the second most common type of neuropathic pain worldwide. The interaction of the virus with the immune system determines the outcome of the infection. Colonization of neurons is essential for virus persistence and pathogenesis. Therefore we are interested in investigating how the human alphaherpesviruses modulate proteins of the immune and nervous system, focusing on cytokines and neurotrophic factors.
During the first two years of the project we have developed tools, established protocols and obtained interesting results regarding how the human alphaherpesviruses modulate chemokine and neurotrophic factor activity. We are characterizing the molecular determinants of the interaction between viral chemokine binding proteins (vCKBP) expressed by HSV-1 and HSV-2 and chemokines, and generating recombinant viruses lacking this activity. In the next funding period we will investigate the role of the vCKBP in vivo. We have also discovered the first VZV protein with the ability to bind and enhance chemokine activity. Since chemokines orchestrate leukocyte migration and VZV infects leukocytes to spread within the host to cause disease, we hypothesise that the enhancement of chemotaxis may facilitate the infection of leukocytes and thereby spread and pathogenesis. Since VZV is human specific we have derived human peripheral neurons from inducible pluripotent stem cells.
During this period the fellow has received the support of the Host Institution, Hannover Medical School (MHH), to establish his independent line of research and to integrate in the local scientific community. The fellow’s group at present is formed by one postdoctoral fellow, three PhD students and one technician. The laboratory is fully equipped to perform the required experiments and the group also has access to core facilities at the MHH, the Twincore and the University of Veterinary Medicine Hannover, Foundation (TiHo).
Shortly after his arrival the fellow joined two research networks, the Collaborative Research Centre 900 and the Niedersachsen-Research Network on Neuroinfectiology (N-RENNT). The former aims at understanding the mechanisms of persistence of chronic pathogens to obtain better therapeutic strategies. N-RENNT focuses on pathogens that infect the nervous system. Participation in these networks fostered the establishment of several scientific collaborations. The fellow is also an active member of the interdisciplinary graduate schools “Hannover Biomedical Research School” of the MHH and “Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology, and Translational Medicine” of the TiHo. Within these Graduate Schools the fellow teaches, supervises and mentors the next generation of international scientists. He has also recently been invited to support a Commission to facilitate the integration of International Faculty members within the MHH. Overall, the Grant has facilitated the integration of the fellow at the MHH and his future consolidation as a permanent Faculty member.

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Life Sciences
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