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Arf GTPases Define BST-2-Independent Pathways for HIV-1 Assembly and Release.

Adam Smith1,2, Dominique Dotson1,2, Jessica Sutton1,2

  • 1Department of Microbiology, Immunology, and Physiology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA.

Viruses
|January 28, 2026
PubMed
Summary
This summary is machine-generated.

ADP-ribosylation factors (Arf1 and Arf6) are crucial for HIV-1 assembly and release. These GTPases regulate viral protein trafficking, essential for efficient virion production, independent of BST-2 antagonism.

Keywords:
ADP-ribosylation factorArf1Arf6BST-2HIV-1 Gagmembrane traffickingvirion releasevirus assembly

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Area of Science:

  • Cell Biology
  • Virology
  • Molecular Biology

Background:

  • ADP-ribosylation factors (Arf) are small GTPases regulating membrane trafficking.
  • Arf1 and Arf6 are implicated in the HIV-1 life cycle, but their precise roles in assembly and release are unclear.

Purpose of the Study:

  • To elucidate the specific roles of Arf1 and Arf6 in HIV-1 Gag polyprotein trafficking, assembly, and virion production.
  • To investigate whether Arf1 and Arf6 functions in HIV-1 release are linked to the host restriction factor BST-2.

Main Methods:

  • Utilized GTP-locked and GDP-locked mutants of Arf1 and Arf6 to perturb their functions.
  • Examined the effects of Arf perturbation on HIV-1 Gag polyprotein trafficking, association with membranes, and accumulation at the plasma membrane.
  • Assessed virion production and Gag localization upon manipulation of Arf1 cycling via AGAP1.
  • Evaluated the impact of Arf1 and Arf6 disruption on BST-2 expression, surface levels, and distribution.

Main Results:

  • Perturbing Arf1 function with mutants significantly reduced HIV-1 release and impaired Gag trafficking and plasma membrane accumulation.
  • Arf1 cycling between GTP- and GDP-bound states is essential for productive Gag trafficking.
  • Constitutively active Arf6 misrouted Gag and suppressed virion release.
  • Arf1 or Arf6 disruption did not affect BST-2 levels or localization.

Conclusions:

  • Arf1 and Arf6 GTPases are critical host factors for efficient HIV-1 assembly and virion release.
  • These Arf-mediated trafficking pathways are essential for Gag polyprotein transport and virus production.
  • The functions of Arf1 and Arf6 in HIV-1 assembly are independent of BST-2 antagonism.