2. Academic Validation
  3. A conserved role for AKT in the replication of emerging flaviviruses in vertebrates and vectors

A conserved role for AKT in the replication of emerging flaviviruses in vertebrates and vectors

  • Virus Res. 2024 Oct:348:199447. doi: 10.1016/j.virusres.2024.199447.
Blanca Palmero Casanova 1,  Laura Albentosa González 2,  Kevin Maringer 3,  Rosario Sabariegos 4,  Antonio Mas 5
Affiliations

Affiliations

  • 1 Instituto de Investigación Biomédica de la UCLM (IB-UCLM), C/Almansa 14, 02008 Albacete, Spain.
  • 2 Instituto de Investigación Biomédica de la UCLM (IB-UCLM), C/Almansa 14, 02008 Albacete, Spain; Facultad de farmacia, Universidad de Castilla-La Mancha, Av. Dr. José María Sánchez Ibáñez, s/n, 02008 Albacete, Spain.
  • 3 The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, UK.
  • 4 Instituto de Investigación Biomédica de la UCLM (IB-UCLM), C/Almansa 14, 02008 Albacete, Spain; Unidad asociada de Biomedicina UCLM-CSIC. Universidad de Castilla-La Mancha. C/Altagracia 50, 13071 Ciudad Real, Spain; Facultad de Medicina, Universidad de Castilla-La Mancha. C/Almansa 14, 02008 Albacete, Spain.
  • 5 Instituto de Investigación Biomédica de la UCLM (IB-UCLM), C/Almansa 14, 02008 Albacete, Spain; Facultad de farmacia, Universidad de Castilla-La Mancha, Av. Dr. José María Sánchez Ibáñez, s/n, 02008 Albacete, Spain; Unidad asociada de Biomedicina UCLM-CSIC. Universidad de Castilla-La Mancha. C/Altagracia 50, 13071 Ciudad Real, Spain. Electronic address: antonio.mas@uclm.es.
PMID: 39117146 DOI: 10.1016/j.virusres.2024.199447
Abstract

One third of all emerging infectious diseases are vector-borne, with no licensed Antiviral therapies available against any vector-borne viruses. Zika virus and Usutu virus are two emerging flaviviruses transmitted primarily by mosquitoes. These viruses modulate different host pathways, including the PI3K/Akt/mTOR pathway. Here, we report the effect on ZIKV and USUV replication of two Akt inhibitors, Miransertib (ARQ-092, allosteric inhibitor) and Capivasertib (AZD5363, competitive inhibitor) in different mammalian and mosquito cell lines. Miransertib showed a stronger inhibitory effect against ZIKV and USUV than Capivasertib in mammalian cells, while Capivasertib showed a stronger effect in mosquito cells. These findings indicate that Akt plays a conserved role in Flavivirus infection, in both the vertebrate host and invertebrate vector. Nevertheless, the specific function of Akt may vary depending on the host species. These findings indicate that Akt may be playing a conserved role in Flavivirus infection in both, the vertebrate host and the invertebrate vector. However, the specific function of Akt may vary depending on the host species. A better understanding of virus-host interactions is therefore required to develop new treatments to prevent human disease and new approaches to control transmission by insect vectors.

Keywords

AKT; AKT inhibitors; Confocal microscopy; Flavivirus; Mammalian cell line; Mosquito cell line; NS5; Protein-protein interactions; USUV; Virus replication; ZIKV.

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