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A peptide derived from sorting nexin 1 inhibits HPV16 entry, retrograde trafficking, and L2 membrane spanning

Shuaizhi Li1, Zachary L Williamson2, Matthew A Christofferson1

  • 1Department of Immunobiology, University of Arizona, Tucson, AZ, USA.

Tumour Virus Research
|June 23, 2024
PubMed

Insights

The peptide SNX1.3 effectively inhibits human papillomavirus (HPV) infection by blocking viral genome trafficking and endocytosis. This discovery offers a potential new strategy for targeting HPV-related cancers.

Area of Science:

  • Virology
  • Cell Biology
  • Cancer Research

Background:

  • High-risk human papillomavirus (HPV) causes nearly all cervical cancers and a significant portion of other human cancers.
  • HPV infection relies on the viral genome accessing host cell nuclei, a process mediated by the minor capsid protein L2.
  • Retrograde trafficking pathways are crucial for HPV nuclear entry.

Purpose of the Study:

  • To investigate the effect of the cell-permeable peptide SNX1.3 on HPV16 infection.
  • To determine if SNX1.3, known to inhibit EGFR trafficking, impacts HPV16 entry and intracellular transport.

Main Methods:

  • Utilized SNX1.3, a peptide derived from sorting nexin 1 (SNX1), in HPV16 infection models.
  • Assessed the impact of SNX1.3 on virion endocytosis, retrograde trafficking, Golgi localization, and L2 protein function.
  • Monitored cell proliferation and post-Golgi trafficking to rule out off-target effects.

Main Results:

  • SNX1.3 significantly inhibited HPV16 infection by delaying endocytosis and blocking retrograde trafficking to the Golgi.
  • The peptide impaired the membrane-spanning function of the HPV minor capsid protein L2.
  • SNX1.3 did not affect cell proliferation or post-Golgi trafficking of HPV16.

Conclusions:

  • SNX1.3 is a potent inhibitor of HPV16 infection, acting on early entry and trafficking steps.
  • The findings highlight the role of SNX1-mediated retrograde trafficking in HPV infection.
  • Further research into SNX1.3's mechanism and its interaction with EGFR signaling could lead to novel antiviral therapies.
Keywords:
HPV16L2Membrane spanningMinor capsid proteinRetrograde traffickingSNX-BARSNX1Sorting nexin 1Viral entry

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