A Ran-binding protein facilitates nuclear import of human papillomavirus type 16.

Kun-Yi Lai,Inci Aydin,Matteo Rizzato,Ruth Villalonga-Planells,Mario Schelhaas,Hannes C A Drexler,Craig Meyers

doi:10.1371/journal.ppat.1009580

Kun-Yi Lai, Inci Aydin + Show 5 more

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https://doi.org/10.1371/journal.ppat.1009580

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Abstract

Human papillomaviruses (HPVs) utilize an atypical mode of nuclear import during cell entry. Residing in the Golgi apparatus until mitosis onset, a subviral complex composed of the minor capsid protein L2 and viral DNA (L2/vDNA) is imported into the nucleus after nuclear envelope breakdown by associating with mitotic chromatin. In this complex, L2 plays a crucial role in the interactions with cellular factors that enable delivery and ultimately tethering of the viral genome to mitotic chromatin. To date, the cellular proteins facilitating these steps remain unknown. Here, we addressed which cellular proteins may be required for this process. Using label-free mass spectrometry, biochemical assays, microscopy, and functional virological assays, we discovered that L2 engages a hitherto unknown protein complex of Ran-binding protein 10 (RanBP10), karyopherin alpha2 (KPNA2), and dynein light chain DYNLT3 to facilitate transport towards mitotic chromatin. Thus, our study not only identifies novel cellular interactors and mechanism that facilitate a poorly understood step in HPV entry, but also a novel cellular transport complex.

Highlights

Human papillomaviruses (HPVs) are a large family of small non-enveloped DNA viruses
Using label-free mass spectrometry, biochemical assays, microscopy, and functional virological assays, we discovered that L2 engages a hitherto unknown protein complex of Ran-binding protein 10 (RanBP10), karyopherin alpha2 (KPNA2), and dynein light chain DYNLT3 to facilitate transport towards mitotic chromatin
We identified for the first time cellular proteins that interacted with L2 for nuclear import

Summary

Introduction

Human papillomaviruses (HPVs) are a large family of small non-enveloped DNA viruses. Their icosahedral (T = 7) capsids are composed of 72 pentameric capsomers of the major capsid protein L1 and up to 72 molecules of the minor capsid protein L2 [1,2,3,4]. HPVs type-dependently infect skin or mucosal epithelia [6,7,8]. Infection of HPVs may cause proliferative lesions such as benign warts, or malignant invasive cancers. HPV type 16 and 18 are the etiological agents of cervical cancers [9,10,11]. HPV16 and HPV18 are considered as high-risk types for the development of anogenital cancers, and are amongst the primary targets for vaccination [12]

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