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. 2013 Jan;87(2):1270-3.
doi: 10.1128/JVI.01991-12. Epub 2012 Oct 31.

SNX17 facilitates infection with diverse papillomavirus types

Martina Bergant  1 , Lawrence Banks
Affiliations

SNX17 facilitates infection with diverse papillomavirus types

Martina Bergant et al. J Virol. 2013 Jan.

Abstract

Previous studies have shown that the human papillomavirus type 16 (HPV-16) L2 capsid protein plays an essential role in viral infection, in part through its interaction with sorting nexin 17 (SNX17). We now show that this interaction between L2 and SNX17 is conserved across multiple PV types. Furthermore, we demonstrate that SNX17 is essential for infection with all PV types analyzed, indicating an evolutionarily highly conserved virus entry mechanism.

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Figures

Fig 1
Fig 1
SNX17 interacts with PV L2 proteins by employing one consensus NPxY/F motif. (A) Endogenous SNX17 was extracted from HEK293 cells and subjected to pulldown assays with GST–HPV-11 L2, GST–HPV-16 L2, GST–BPV-1 L2, GST–HPV-5 L2, and GST–SfPV-1 L2 fusion proteins. Bound proteins and cell extracts were analyzed by immunoblotting using anti-SNX17 antibodies. Arrows on the Ponceau-stained gels show levels of purified GST-fused proteins used in the pulldown assay. (B) Wild-type HPV-16 L2 and two L2 mutants with mutations in the consensus SNX17 binding sites (160NPTF and 254NPAY) were transiently expressed in HEK293 cells. After 24 h, proteins were extracted and subjected to pulldown with GST-SNX17 fusion protein. Bound proteins and cell extracts were analyzed by immunoblotting using an anti-HA antibody. In all GST binding experiments, GST proteins were used as a negative control. Asterisks denote a nonspecific band recognized by the anti-HA antibody. Numbers at the gel borders are molecular sizes, in kilodaltons.
Fig 2
Fig 2
Loss of SNX17 inhibits papillomavirus infection. (A) Conservation of the extended consensus SNX17 binding site, (F/Y)xNPAF/Y in some selected HPV types, bovine papillomavirus type 1 (BPV-1), cottontail rabbit papillomavirus type 1 (SfPV-1), and Mus musculus papillomavirus type 1 (MmuPV-1). (B) HaCaT cells were transfected with siSNX17 or siHPV-18 E6/E7 (siCTRL) for 48 h and then exposed to PsVs of different PV types carrying a luciferase reporter plasmid. MCV was used as an infection control. A representative immunoblot shows the level of SNX17 expression obtained with siRNA silencing, and equivalent levels of SNX17 knockdown were verified in all of the assays where α-actinin was used as a loading control. (C) HaCaT, HEK293, and U2OS cells were transfected with siSNX17 or siCTRL for 48 h and then exposed to HPV-16 or MCV PsVs carrying a luciferase reporter plasmid. In all experiments, the level of luciferase activity was evaluated 48 h postinfection in triplicate by luminometry. Obtained values were corrected for background luminescence and normalized to siCTRL-transfected cells infected with the same type of pseudovirus. Results are expressed as means ± standard deviations of at least four independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
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