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Role of the lysosomal protein LAMP2 in the AD-like phenotype induced by HSV-1: Study of the LAMP2 interactome in virus infected neurons

18th national competition for scientific and technical research

Interactome: pathological implications

Senior Researcher : María Jesús Bullido Gómez-Heras

Research Centre or Institution : Centro de Biología Molecular "Severo Ochoa". CSIC-Universidad Autónoma de Madrid


The evidence supporting a role for herpes simplex 1 virus (HSV-1) in the pathogenesis of Alzheimer's disease (AD) continues to grow, as do the number of studies to identify the underlying mechanisms. Functional genomic analysis of a cell model of infection developed in our laboratory pointed to LAMP2, a major lysosomal membrane protein, as a possible mediator of the neurodegenerative process induced by the virus. This observation was reinforced by the genetic association of LAMP2 variants with AD risk. In this project we are studying the mechanisms by which LAMP2 participates in HSV-1 induced neurodegeneration. 

We have found that LAMP2 deficiency impairs HSV‑1 infection, as well as the hyperphosphorylation of tau and the inhibition of Aβ secretion induced by the virus. Among the cellular mechanisms potentially mediating these effects, we are studying the role of intracellular cholesterol homeostasis. This mechanism is of special interest to this project, because LAMP2 participates in the mobilization of lysosomal cholesterol and because in our model the decrease of cellular cholesterol partially reverses the virus-induced accumulation of hyperphosphorylated tau.

In addition, we continue to develop the analysis of LAMP2 viral interactoma in order to identify viral proteins capable of interacting with LAMP2 and modifying its function. To do this, we are conducting coimmunoprecipitation (co-IP) experiments with LAMP2-specific antibodies followed by proteomic analysis using mass spectrometry. Recent data has shown two viral proteins specifically immunoprecipitated with LAMP2 antibody. We are currently designing a series of experiments to confirm these interactions and to get insight into the viral and cellular processes to which the interaction could affect.

In sum, the results obtained to date suggest that viral  proteins directly interact with LAMP2, and continues to support this lysosomal protein as an ideal candidate to mediate the neurodegeneration induced by infection with HSV‑1.


Scientific Production
Magazine Articles -
Communications at national conferences 2
Communications at international conferences 1


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