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

by Snijder, Berend , Samperio Ventayol, Pilar , Becker, Miriam , Kann, Michael , Schiller, John T. , Pelkmans, Lucas , Day, Patricia M. , Aydin, Inci , Weber, Susanne , Schelhaas, Mario , Kühbacher, Andreas , Helenius, Ari

in Active Transport, Cell Nucleus / Biology and Life Sciences / Care and treatment / Cell division / Cell Nucleus - metabolism / Cells, Cultured / Colleges & universities / Complications and side effects / Deoxyribonucleic acid / Development and progression / DNA / DNA viruses / DNA, Viral - genetics / Gene expression / Genetic aspects / Genomes / Heparan sulfate / Human papillomavirus / Human papillomavirus 16 - genetics / Humans / Infections / Life Sciences / Microbiology and Parasitology / Microscopy / Mitosis - physiology / Nuclear Envelope - metabolism / Oncogene Proteins, Viral - genetics / Papillomavirus infections / Patient outcomes / Proteins / Risk factors / RNA Interference / Stem cells / Tumors / Viral infections / Viruses

2014

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

2014

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

2014

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Journal Article

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

Snijder, Berend,

Samperio Ventayol, Pilar,

Becker, Miriam,

Kann, Michael,

Schiller, John T.,

Pelkmans, Lucas,

Day, Patricia M.,

Aydin, Inci,

Weber, Susanne,

Schelhaas, Mario,

Kühbacher, Andreas,

Helenius, Ari

2014

Overview

A two-step, high-throughput RNAi silencing screen was used to identify host cell factors required during human papillomavirus type 16 (HPV16) infection. Analysis of validated hits implicated a cluster of mitotic genes and revealed a previously undetermined mechanism for import of the viral DNA (vDNA) into the nucleus. In interphase cells, viruses were endocytosed, routed to the perinuclear area, and uncoated, but the vDNA failed to be imported into the nucleus. Upon nuclear envelope perforation in interphase cells HPV16 infection occured. During mitosis, the vDNA and L2 associated with host cell chromatin on the metaphase plate. Hence, we propose that HPV16 requires nuclear envelope breakdown during mitosis for access of the vDNA to the nucleoplasm. The results accentuate the value of genes found by RNAi screens for investigation of viral infections. The list of cell functions required during HPV16 infection will, moreover, provide a resource for future virus-host cell interaction studies.

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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

Active Transport, Cell Nucleus

/ Biology and Life Sciences

/ Care and treatment

/ Cell division

/ Cell Nucleus - metabolism

/ Cells, Cultured

/ Colleges & universities