Phosphorylation of HPV-16 L2 Contributes To Efficient Virus Infectious EntryRobert L. Garcea
, Michael P. Myers
, Martina Bergant Marušič
, David Pim
, Paola Massimi
, Justyna Broniarczyk
, Lawrence Banks
, 2019, izvirni znanstveni članek
Opis: The Human Papillomavirus (HPV) capsid comprises two viral proteins, L1 and L2, with the L2 component being essential to ensure efficient endocytic transport of incoming viral genomes. Several studies have previously reported that L1 and L2 are post-translationally modified, but it is uncertain whether these modifications affect HPV infectious entry. Using a proteomic screen, we identified a highly conserved phospho-acceptor site on the HPV-16 and BPV-1 L2 proteins. The phospho-modification of L2, and its presence in HPV pseudovirions (PsVs), was confirmed using anti-phospho L2-specific antibodies. Mutation of the phospho-acceptor sites of both HPV-16 and BPV-1 L2 resulted in the production of infectious virus particles, with no differences in efficiency of packaging the reporter DNA. However, these mutated PsVs showed marked defects in infectious entry. Further analysis revealed a defect in uncoating, characterized by a delay in the exposure of a conformational epitope on L1 that indicates capsid uncoating. This uncoating defect was accompanied by a delay in the proteolysis of both L1 and L2 in mutated HPV-16 PsVs. Taken together, these studies indicate that phosphorylation of L2 during virus assembly plays an important role in optimal uncoating of virions during infection, suggesting that phosphorylation of the viral capsid proteins contributes to infectious entry.
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Povzetek najdenega: ...HPV, L2, infection, protein phosphorylation...
Ključne besede: HPV, L2, infection, protein phosphorylation
Objavljeno: 05.06.2019; Ogledov: 2536; Prenosov: 0
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