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HIV-1 and Its Strategy for Hiding Viral cDNA from STING-Mediated Innate Immunity.

Anna Mashkovskaia1,2,3, Yulia Agapkina1,2, Tatiana Oretskaya2

  • 1Chemistry Department, Lomonosov Moscow State University, 119992 Moscow, Russia.

International Journal of Molecular Sciences
|December 11, 2025
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Human immunodeficiency virus type 1 (HIV-1) evades immune detection by hiding viral DNA from cytosolic sensors. Understanding these evasion mechanisms could lead to new antiviral therapies targeting HIV-1 innate immune suppression.

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HIVSTINGcGAScytosolic DNA sensorinnate immunity

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Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) activates cytosolic DNA sensors, like cGAS-STING, triggering interferon production.
  • Viral RNA reverse transcription into cDNA in the cytoplasm is the main source of this activation.
  • HIV-1 exhibits lower cytosolic DNA sensor activation compared to DNA viruses or HIV-2.

Purpose of the Study:

  • To review mechanisms HIV-1 uses to evade cytosolic DNA sensor detection.
  • To identify potential therapeutic targets for novel antiviral strategies.

Main Methods:

  • Literature review of studies on HIV-1 innate immune evasion.
  • Analysis of mechanisms disrupting the cGAS-STING pathway.

Main Results:

  • HIV-1 actively conceals viral cDNA from cytosolic DNA sensors.
  • Specific mechanisms employed by HIV-1 to disrupt innate immune recognition are detailed.
  • HIV-1's evasion strategies are more effective than those of HIV-2.

Conclusions:

  • HIV-1 employs sophisticated mechanisms to evade innate immune sensing, particularly the cGAS-STING pathway.
  • Deciphering these viral evasion tactics offers opportunities for developing new antiviral interventions.
  • Targeting HIV-1's immune evasion could be a promising strategy for future therapies.