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Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
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Cellular Responses to Flavivirus Infections: Stress Signaling at the Crossroads of Host Defense and Virus Infection

Pheonah Badu1,2, Elianna T Cruz González1,2, Cara T Pager1,2

  • 1Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222, USA.

Viruses
|July 28, 2026
PubMed

Insights

Flaviviruses trigger complex cellular stress responses to survive, but viruses like Dengue and Zika have evolved ways to overcome these defenses. Understanding these interactions is key to developing new antiviral treatments.

Area of Science:

  • Virology
  • Cellular Biology
  • Immunology

Background:

  • Flaviviruses, including Dengue, Zika, and West Nile viruses, induce significant cellular stress responses.
  • Key pathways involved include the unfolded protein response (UPR), integrated stress response (ISR), apoptosis, autophagy, and antiviral immunity.
  • These responses aim to protect cells and limit viral spread, but viruses have evolved mechanisms to subvert them.

Purpose of the Study:

  • To review the cellular stress pathways activated during flavivirus infections.
  • To examine viral subversion strategies targeting these pathways.
  • To explore the interplay and synergy among different stress response pathways.

Main Methods:

  • Literature review of cellular stress responses in flavivirus infections.
  • Analysis of viral mechanisms for subverting host cell defenses.
  • Synthesis of current understanding on pathway interactions.

Main Results:

  • Flaviviruses activate a range of cellular stress responses, including UPR, ISR, apoptosis, and autophagy.
  • Viruses employ sophisticated strategies, often involving viral proteins, to evade or manipulate these cellular defenses.
  • Emerging evidence indicates dynamic interplay and crosstalk between previously distinct stress response pathways.

Conclusions:

  • Cellular stress responses are crucial in the host-pathogen interaction during flavivirus infections.
  • Viral subversion of these pathways is essential for successful infection.
  • Further investigation into the synergistic actions of these pathways is needed to develop effective antiviral strategies.
Keywords:
apoptosisautophagyflavivirusesimmune responseintegrated stress responseunfolded protein response

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