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Juan Martin Serrano

Professor

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    Research interests

    The last step in retroviral life cycle is the separation of the nascent viral particle from the infected cell. HIV-1 and other retroviruses encode a so-called Late Budding domain (L-domain) whose mutation induces the accumulation of immature virions that remain tethered to the plasma membrane by a membranous stalk. Work by our group and other laboratories has identified the cellular protein Tsg101 as the cellular partner that facilitates HIV-1 and Ebola virus budding thorough the interaction with a highly conserved aminoacid motif (PTAP) in the L-domain of these pathogens. Subsequently, it has been shown that other viruses that include HIV-2, HTLV and Lassa fever virus also require Tsg101 for particle budding, thus emphasizing the importance of this protein in human disease. Tsg101, the mammalian orthologue of the yeast protein Vps23, is one of the subunits of a 350 kd complex (endosomal sorting complex required for transport-I, ESCRT-I) which also includes Vps28 and Vps37. Tsg101 is a component of the class E pathway and is required both for the budding of viruses that encode PTAP type L-domains and the topologically equivalent process of vesicle budding into Multivesicular Bodies (MVB). Recent work by our laboratory and others has identified 19 human genes of the class E pathway that participate in budding of highly divergent enveloped viruses and, perhaps, MVB biogenesis. Importantly, a greater understanding of how HIV-1 viruses exploit the host cell to facilitate the budding process could provide opportunities for chemotherapeutic intervention using a completely novel class of antiviral compounds that would be active against a number of human pathogens including HIV-1, HIV-2, Ebola virus, HTLV, Lassa fever virus and essentially any virus that exploits the PTAP/Tsg101 interaction during budding. Our work with the ESCRT proteins has recently led to the discovery of and exciting link between retroviral budding and abscission, the last step in cell division. We have described that Tsg101 and ALIX are recruited to the midbody by Cep55 to mediate the separation of the daughter cells through a mechanism that is topologically similar to HIV-1 budding.

    Research interests (short)

    Retroviral assembly; endosomal sorting; cytokinesis.

    Expertise related to UN Sustainable Development Goals

    In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

    • SDG 3 - Good Health and Well-being

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