Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses

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Certain human papillomaviruses (HPV) are the etiological cause of cervical cancers and other epithelial tumors. Recent advances in the development of anti-HPV vaccines and their increasing deployment provide hope for a significant decrease of these cancers in the future. However, many details of the transmission of HPV between infected and uninfected individuals are still not well understood. In particular, the multistep process of entry into host cells is only partially characterized. Here, we used a systematic RNAi silencing approach to identify host cell proteins required during HPV16 infection, the most prevalent cancer-causing HPV. Our results indicated that HPV entry requires cells to divide. Cell division is important, since it removes the barrier between the nucleoplasm and the cytosol, so that the virus can access the nucleus for transcription and replication. Our study provides new mechanistic insights into the entry process of an important pathogen, and explains why it can only infect the stem cells or transiently amplifying cells of human skin or mucosa. This work also highlights a novel nuclear import strategy for DNA viruses, which typically use the nuclear import machinery to access the nucleoplasm for infection, Thus, HPV entry displays another unique aspect uncommon to most other viruses.

Vyšlo v časopise: Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004162
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004162

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