Publications by authors named "M A Cuesta-Geijo"

African swine fever virus (ASFV) belongs to the family of , part of the group of nucleocytoplasmic large DNA viruses (NCLDV). Little is known about the internalization of ASFV in the host cell and the fusion membrane events that take place at early stages of the infection. Poxviruses, also members of the NCLDV and represented by vaccinia virus (VACV), are large, enveloped, double-stranded DNA viruses.

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The African swine fever virus (ASFV) is strongly dependent on an intact endocytic pathway and a certain cellular membrane remodeling for infection, possibly regulated by the endosomal sorting complexes required for transport (ESCRT). The ESCRT machinery is mainly involved in the coordination of membrane dynamics; hence, several viruses exploit this complex and its accessory proteins VPS4 and ALIX for their own benefit. In this work, we found that shRNA-mediated knockdown of VPS4A decreased ASFV replication and viral titers, and this silencing resulted in an enhanced expression of ESCRT-0 component HRS.

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African swine fever virus (ASFV) encodes more than 150 proteins, most of them of unknown function. We used a high-throughput proteomic analysis to elucidate the interactome of four ASFV proteins, which potentially mediate a critical step of the infection cycle, the fusion and endosomal exit of the virions. Using affinity purification and mass spectrometry, we were able to identify potential interacting partners for those ASFV proteins P34, E199L, MGF360-15R and E248R.

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Ebola virus (EBOV) is a single-strand RNA virus belonging to the family, which has been associated to most Ebola virus disease outbreaks to date, including the West African and the North Kivu epidemics between 2013 and 2022. This unprecedented health emergency prompted the search for effective medical countermeasures. Following up on the carbazole hit identified in our previous studies, we synthetized a new series of compounds, which demonstrated to prevent EBOV infection in cells by acting as virus entry inhibitors.

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Article Synopsis
  • The African swine fever virus (ASFV) enters host cells through a process that involves clathrin/dynamin mediated endocytosis and macropinocytosis, leading to the internalization of the virus.
  • The virus undergoes decapsidation in the acidic environment of late endosomes, exposing its inner membrane, which is essential for interacting and fusing with the endosomal membrane to release viral nucleic acids into the cytoplasm for replication.
  • Specific ASFV proteins (E248R and E199L) interact with cellular proteins like Niemann-Pick C type 1 (NPC1), and disruption of these interactions impairs ASFV infection, indicating the importance of endosomal proteins for successful viral entry and replication
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