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hpv

衛生福利部國民健康署 - 什麼是人類乳突病毒(HPV)?

HPV (human papillomavirus) is a small, non-enveloped double-stranded DNA virus that belongs to the Papovaviridae family. It is the primary etiological agent in cervical cancer and other carcinomas, cutaneous and mucosal papillomas[1][2].

The viral mechanism of HPV infection involves several key steps:

  1. Initial Binding: HPV binds to heparan sulfate proteoglycans (HSPGs) on the basement membrane (BM) exposed after epithelial trauma. This binding is mediated by the L1 major capsid protein[1][2].

  2. Conformational Change: The virus undergoes a conformational change that exposes the N-terminus of the L2 minor capsid protein to furin cleavage. This change is necessary for the virus to interact with the cell surface receptor[1].

  3. Secondary Receptor Interaction: The L1 protein binds to an as yet undetermined cell surface receptor on keratinocytes that have migrated over the BM to close the wound. This interaction is necessary for internalization[1].

  4. Internalization: The virus is internalized via a clathrin-dependent endocytic mechanism, although some HPV types may use alternative uptake pathways such as caveolae-dependent or tetraspanin-enriched domains[2][3].

  5. Endosomal Escape: The virus escapes from the endosome by an L2-dependent mechanism, allowing the viral genome to access the cellular transcription and replication machinery[2].

  6. Nuclear Transport: The viral genome is transported to specific subnuclear domains designated ND10 bodies, where viral gene transcription is initiated[1].

  7. Transcription and Replication: The viral genome is transcribed and replicated in the nucleus, leading to the production of new viral particles[1].

This complex process is characterized by a slow and asynchronous entry process, with the virus residing on the cell surface for an extended period before internalization[1][2].

Citations

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493113/ [2] https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-7-11 [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618609/ [4] https://www.researchgate.net/publication/372042891_Virtual_Screening_of_Kaempferia_galanga_L_Bioactive_Compounds_as_HPV-16_Antiviral_Mechanism_Through_E6_Inhibitor_Activity [5] https://www.mdpi.com/246922