4.8 Article

HPV is a cargo for the COPI sorting complex during virus entry

Journal

SCIENCE ADVANCES
Volume 9, Issue 3, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.adc9830

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During HPV entry, the virus is trafficked through the cell compartments, including the endosome, trans-Golgi network (TGN), and Golgi apparatus. The coat protein complex I (COPI) is identified as a host factor required for HPV infection. The interaction between the cytoplasmic segment of HPV L2 and COPI facilitates the trafficking of HPV through the TGN and Golgi stacks, ultimately reaching the nucleus.
During entry, human papillomavirus (HPV) traffics from the cell surface to the endosome and then to the trans-Golgi network (TGN) and Golgi apparatus. HPV must transit across the TGN/Golgi and exit these compartments to reach the nucleus to cause infection, although how these steps are accomplished is unclear. Combining cel-lular fractionation, unbiased proteomics, and gene knockdown strategies, we identified the coat protein complex I (COPI), a highly conserved protein complex that facilitates retrograde trafficking of cellular cargos, as a host factor required for HPV infection. Upon TGN/Golgi arrival, the cytoplasmic segment of HPV L2 binds directly to COPI. COPI depletion causes the accumulation of HPV in the TGN/Golgi, resembling the fate of a COPI binding-defective L2 mutant. We propose that the L2-COPI interaction drives HPV trafficking through the TGN and Golgi stacks during virus entry. This shows that an incoming virus is a cargo of the COPI complex.

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