WAVE1 and WAVE2 facilitate human papillomavirus-driven actin polymerization during cellular entry.

bioRxiv

Department of Molecular Microbiology & Immunology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States.

Published: October 2024

AI Article Synopsis

  • HPV16, a type of Human Papillomavirus, requires a specific endocytic process involving actin to infect epithelial cells, although the exact mechanisms of this process are not fully understood.
  • This study identifies WAVE1 and WAVE2 proteins as key players in actin polymerization that facilitates HPV16's entry into cells, demonstrating their importance through gene silencing and genome editing techniques.
  • Observations showed that HPV16, WAVE1, WAVE2, and actin localize together on the cell surface, and HPV16 activates the formation of filopodia—extensions of the cell membrane—during the viral entry process, underscoring the role of actin dynamics in viral infection.

Article Abstract

Human PapillomavirusType 16 (HPV16) is an etiological agent of human cancers that requires endocytosis to initiate infection. HPV16 entry into epithelial cells occurs through a non-canonical endocytic pathway that is actin-driven, but it is not well understood how HPV16-cell surface interactions trigger actin reorganization in a way that facilitates entry. This study provides evidence that Wiskott-Aldrich syndrome protein family verprolin-homologous proteins 1 and 2 (WAVE1 and WAVE2) are molecular mediators of the actin polymerization that facilitates HPV endocytosis and intracellular trafficking. We demonstrate through post-transcriptional gene silencing and genome editing that WAVE1 and WAVE2 are critical for efficient HPV16 infection, and that restoration of each in knockout cells rescues HPV16 infection. Cells lacking WAVE1, WAVE2, or both, internalize HPV16 at a significantly reduced rate. Analysis of fluorescently labeled cells exposed to HPV16 and acquired by confocal fluorescence microscopy revealed that HPV16, WAVE1, WAVE2, and actin are all colocalized at the cellular dorsal surface. We also found that HPV16 stimulates WAVE1 and WAVE2-mediated cellular dorsal surface filopodia formation during the viral endocytic process. Taken together, this study provides evidence that the HPV endocytic process needed for infection is controlled by actin reorganization into filopodial protrusions and that this process is mediated by WAVE1 and WAVE2.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565777PMC
http://dx.doi.org/10.1101/2024.10.28.620484DOI Listing

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Department of Molecular Microbiology & Immunology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States.

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  • This study identifies WAVE1 and WAVE2 proteins as key players in actin polymerization that facilitates HPV16's entry into cells, demonstrating their importance through gene silencing and genome editing techniques.
  • Observations showed that HPV16, WAVE1, WAVE2, and actin localize together on the cell surface, and HPV16 activates the formation of filopodia—extensions of the cell membrane—during the viral entry process, underscoring the role of actin dynamics in viral infection.
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