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Abstract

Actin-associated proteins have been implicated in several stages of virus infection. However, the role of myosins, which are actin-dependent molecular motors, during virus infection and pathogenesis is poorly understood. Myosin IXB (Myo9b) is a member of the myosin family abundantly expressed in immune cells. Myo9b displays a RhoGTPase-activating protein domain capable of modulating actin dynamics by inhibiting RhoGTPase activity. To enquire upon Myo9b participation in virus infections, we have silenced Myo9b in U937 and Jurkat cells and infected them with vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped HIV-1. Myo9b-silenced U937 showed a remarkable increase of above ten times more HIV-VSV-G infection than control cells. We observed a similar pattern in Jurkat cell infection with both WT Env and VSV-G-pseudotyped HIV, albeit to a lesser extent. Myo9b-silenced U937 cells presented elevated levels of phosphorylated cofilin, but lower levels of polymerized actin. The use of a RhoA, B and C inhibitor, as well as a Rac1 inhibitor, reduced virus infection. Finally, we have also observed an increment in virus internalization and fusion in cells knockdown for Myo9b, which may explain the increase in virus infection. Taken together, our data suggests that Myo9b might hinder viral entry and infection by controlling the activity of RhoGTPases in immune cells.

Funding
This study was supported by the:
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Award 88887.913459/2023-00)
    • Principle Award Recipient: FelippeEgon Castrignano Camargo
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Award 88887.475141/2020-00)
    • Principle Award Recipient: TaniaCarolina Braga
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Award 88887.335109/2019-00)
    • Principle Award Recipient: TaísMatozo
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 2022-2904)
    • Principle Award Recipient: MarinaJanoni Bayerlein
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 141858/2023-0)
    • Principle Award Recipient: KamillaBatista da Silva Souza
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 133243/2019-2)
    • Principle Award Recipient: LeticiaKogachi
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 304358/2021-5)
    • Principle Award Recipient: FábioLuis Forti
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 420482/2023-7)
    • Principle Award Recipient: FábioLuis Forti
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (Award 2022/12337-9)
    • Principle Award Recipient: YuliThamires Magalhães
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (Award 2022/04243-4)
    • Principle Award Recipient: FábioLuis Forti
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (Award 2022/12443-3)
    • Principle Award Recipient: BrunaCunha de Alencar
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (Award 2014/23225-0)
    • Principle Award Recipient: BrunaCunha de Alencar
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
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2025-04-01
2025-04-21
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