Despite the advances against infectious diseases, morbidity and mortality still pose a very high social and economic impact. Viruses have developed a plethora of strategies to modulate the host. The main goal of my research is to investigate these strategies in order to understand viral immunomodulation, neuromodulation and pathogenesis. This will permit us to develop better intervention approaches to combat viral infections and their role in neuropathies. Due to their high prevalence and adaptation to their hosts, I will focus on relevant human pathogens within the Herpesviridae family: herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively) and varicella zoster virus (VZV). These viruses establish latency in sensory ganglia of the peripheral nervous system. The mechanisms that allow the colonization of the nervous system by these viruses are unknown. The interplay between the virus and the immune system is relevant for persistence and pathogenesis.Chemokines and neurotrophic factors play a relevant role in the crosstalk between the immune and nervous systems. We have recently discovered the first mechanism employed by a virus, HSV, to modulate both sets of proteins. This novel strategy may be relevant for HSV spread, colonization of the nervous system and pathogenesis. Other relevant human pathogens, such as VZV, may express modulators of chemokines and/or neurotrophic factors. These hypotheses will be addressed using molecular, cell biology, functional assays, and mouse models.My previous experience in viral modulation, the multidisciplinary approach of the project and the interdisciplinary environment of the host institution will ensure the feasibility of this proposal. We will discover novel viral mechanisms of immune, neuromodulation and pathogenesis providing relevant insights on the cellular processes involved. The results will permit developing better intervention approaches to combat viral infections and their role in neuropathies.