Visual Universitätsmedizin Mainz

Cell biology of human papillomaviruses (Florin Laboratory)

 

 

The Florin laboratory investigates human papillomavirus (HPV) entry, morphogenesis, and cellular defense mechanisms. HPV is a non-enveloped DNA tumor virus that infects skin and mucosa. The most oncogenic subtype, HPV16, causes various types of cancer, including cervical, anal, and head and neck cancers.

 

Lab Members

PD Dr. rer. nat. Florin
PD Dr. rer. nat. Luise Florin
Function: Principal Investigator

06131 17-9083
06131 17-9021
lflorin@uni-mainz.de

Boukhallouk
Fatima Boukhallouk
Function: Medical Technician

06131 17-9208
06131 17-9021
bouk@uni-mainz.de

Fast
Laura Fast
Function: Ph.D. Student

17-9336
17-9234
laura.fast@uni-mainz.de

Mikulicic
Snjezana Mikulicic
Function: Ph.D. Student

17-9336
17-9234
snmikuli@uni-mainz.de

Dr. rer. nat. Wüstenhagen
Dr. rer. nat. Elena Wüstenhagen
Function: Postdoc

17-9327
17-9234
elwueste@uni-mainz.de

Fritzen
Anna Fritzen
Funktionen: Medical Doctoral Student

17-9327
17-9234
afritzen@students.uni-mainz.de

Gräßel
Linda Gräßel
Funktionen: Medical Doctoral Student

17-9327
17-9234
lgraesse@students.uni-mainz.de

Schweiger
Linda Schweiger
Funktionen:  Medical Doctoral Student

17-9336
17-9234
lischwei@students.uni-mainz.de

Current Research and Publications

Our focus is to better understand how HPV enters cells. Our previous studies have revealed that HPV16 endocytosis occurs via tetraspanin-enriched microdomains through a novel clathrin- and caveolin-independent entry pathway. Specifically, (TIRF) microscopy of live cells, electron microscopy and infection analyses revealed that the tetraspanin CD151 mediates HPV endocytosis by interaction with laminin-binding integrins and integration of the papillomavirus-receptor complex into cell entry platforms. Our aim is to contribute to a more in depth understanding of the endocytic trafficking pathway that controls HPV entry and infection by building upon novel data that link tetraspanins and its adaptor proteins to HPV infection.

Biophysical and functional analyses with the minor capsid protein L2 identified a direct interaction of the viral protein with cellular interaction partners such as cellular cytoskeletal proteins, transcription factors, and the small ubiquitin-like modifier (SUMO), which is indispensable for the delivery of viral DNA to nuclear structures and viral gene regulation. In addition, we recently showed the role of diverse host cell proteins during infection and their potential as new antiviral Targets.

 

Fast LA, Lieber D, Lang T, Florin L. (2017): Tetraspanins in infections by human cytomegalo-and papillomaviruses. Biochem Soc Trans. Apr 15;45(2):489-497.Review.

 

Schulze U, Brast S, Grabner A, Albiker C, Snieder B, Holle S, Schlatter E, Schröter R, Pavenstädt H, Hermann E, Lambert C, Spoden GA, Florin L, Saftig P, Ciarimboli G. (2017): Tetraspanin CD63 controls basolateral sorting of organic cation transporter 2 in renal proximal tubules. FASEB J. Apr;31(4):1421-1433.

 

Wüstenhagen E, Hampe L, Boukhallouk F, Schneider MA, Spoden GA, Negwer I, Koynov K, Kast WM, Florin L. (2016): The cytoskeletal adaptor obscurin-like 1 interacts with the HPV16 capsid protein L2 and is required for HPV16 endocytosis. J Virol. Nov;90(23):10629-10641.

 

Gräßel L, Fast LA, Scheffer KD, Boukhallouk F, Spoden GA, Tenzer S, Boller K, Bago R, Rajesh S, Overduin M, Berditchevski F, Florin L. (2016): The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses. Sci Rep. Aug 31;6:32337.

 

Hochdorfer D, Florin L, Sinzger C, Lieber D. (2016): Tetraspanin CD151 Promotes Initial Events in Human Cytomegalovirus Infection. J. Virol. Jun 24;90(14):6430-42.

 

Kroemmelbein N, Wiebusch L, Schiedner G, Buescher N, Sauer C, Florin L, Sehn E, Wolfrum U, Plachter B. (2016): Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication. VIRUSES-BASEL: 8(2).

 

Bund T, Spoden GA, Koynov K, Hellmann N, Boukhallouk F, Arnold P, Hinderberger D, Florin L. (2014): An L2 SUMO interacting motif is important for PML localization and infection of human papillomavirus type 16. Cellular Microbiology. 16(8): 1179-1200.

 

Homsi Y, Schloetel JG, Scheffer KD, Schmidt TH, Destainville N, Florin L, Lang T. (2014): The Extracellular delta-Domain is Essential for the Formation of CD81 Tetraspanin Webs. Biophysical Journal. 107(1): 100-113.

 

Scheffer KD, Berditchevski F, Florin L. (2014): The Tetraspanin CD151 in Papillomavirus Infection: Viruses-Basel.  6(2): 893-908. Review.

 

Mueller KH, Spoden GA, Scheffer KD, Brunnhoefer R, De Brabander JK, Maier ME, Florin L, Muller CP. (2014): Inhibition by Cellular Vacuolar ATPase Impairs Human Papillomavirus Uncoating and Infection: Antimicrobial Agents and Chemotherapie 58 (5): 2905-2911.

 

Theisen LL, Erdelmeier CAJ, Spoden GA, Boukhallouk F, Sausy A, Florin L, Muller CP. (2014): Tannins from Hamamelis virginiana Bark Extract: Characterization and Improvement of the Antiviral Efficacy against Influenza A Virus and Human Papillomavirus: PLOS ONE. ; 9 (1).

 

Scheffer KD, Popa-Wagner R, Florin L. (2013): Isolation and characterization of pathogen-bearing endosomes enable analysis of endosomal escape and identification of new cellular cofactors of infection. Beitrag in: Methods in Molecular Biology. Herausgeber: Susanne M. Bailer, Diana Lieber, Springer , S.101-113.

 

Spoden G, Kuehling L, Cordes N, Frenzel B, Sapp M, Boller K, Florin L, Schelhaas M. (2013): Human Papillomavirus Types 16, 18, and 31 Share Similar Endocytic Requirements for Entry. J Virol; 87 (13): 7765-7773.

 

Schneider MA, Scheffer KD, Bund T, Boukhallouk F, Lambert C, Cotarelo C, Pflugfelder GO, Florin L, Spoden GA. (2013): The Transcription Factors TBX2 and TBX3 Interact with Human Papillomavirus 16 (HPV16) L2 and Repress the Long Control Region of HPVs: J Virol; 87(8): 4461-4474.

 

Scheffer KD, Gawlitza A, Spoden GA, Zhang XA, Lambert C, Berditchevski F, Florin L. (2013):Tetraspanin CD151 Mediates Papillomavirus Type 16 Endocytosis. J Virol, 87(6): 3435-3446.

 

Florin L, Sapp M, Spoden GA. (2012): Host-cell factors involved in papillomavirus entry. Med Microbiol Immunol 201(4):437-48. Review.

 

Foersch S, Heimann A, Ayyad A, Spoden GA, Florin L, Mpoukouvalas K, Kiesslich R, Kempski O, Goetz M, Charalampaki P. (2012): Confocal Laser Endomicroscopy for Diagnosis and Histomorphologic Imaging of Brain Tumors In Vivo. PLos ONE, 7(7).

 

Popa-Wagner R, Porwal M, Kann M, Reuss M, Weimer M, Florin L, Kleinschmidt JA. (2012): Impact of VP1-specific protein sequence motifs on AAV2 intracellular trafficking and nuclear entry. J Virol, 86 (17):9163-74.

 

Spoden GA, Besold K, Krauter S, Plachter B, Hanik N, Kilbinger AF, Lambert C, Florin L. (2012): Polyethylenimine Is a Strong Inhibitor of Human Papillomavirus and Cytomegalovirus Infection. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 5 (1): 75-82.

 

Schneider MA, Spoden GA, Florin L, Lambert C. (2011):Identification of the dynein light chains required for human papillomavirus infection.Cellular Microbiology, 13(1): 32-46.

 

Spoden G, Freitag K, Husmann M, Boller K, Sapp M, Lambert C, Florin L. (2008): Clathrin- and Caveolin-independent entry of human papillomavirus Type 16 – Involvement of tetraspanin-enriched microdomains (TEMs). PLos ONE, 3(10):e3313.

 

Selinka HC, Florin L, Patel HD, Freitag K, Schmidtke M, Makarov VA, Sapp M. (2007): Inhibition of transfer to secondary receptors by heparan sulfate-binding drug or antibody induces noninfectious uptake of human papillomavirus. J Virol. 81(20):10970-80.

 

Florin L, Becker KA, Lambert C, Nowak T, Sapp C, Strand D, Streeck RE, Sapp M. (2006): Identification of a dynein interacting domain in the papillomavirus minor capsid protein L2. J Virol. 80(13):6691-6.

 

Kaemper, N, Day, PM, Nowak, T., Selinka, HC, Florin L, Bolscher, JG, Hilbig, L, Schiller, JT, and Sapp, M. (2006): A Membrane-destabilizing Peptide in capsid Protein L2 required for egress of papillomavirus genomes from endosomes. J. Virol. 80:759-68.

 

Florin L, Becker KA, Sapp C, Lambert C, Sirma H, Müller M, Streeck RE, and Sapp, M. (2004): Nuclear translocation of papillomavirus minor capsid protein L2 requires Hsc70. J. Virol. 78:5546-5553.

 

Becker KA, Florin L, Sapp C, Maul GG, Sapp M. (2004): Nuclear localization but not PML protein is required for incorporation of the papillomavirus minor capsid protein L2 into virus-like particles. J Virol. 78:1121-8.

 

Becker KA, Florin L, Sapp C, Sapp M. (2003): Dissection of human papillomavirus type 33 L2 domains involved in nuclear domains (ND) 10 homing and reorganization. Virology 314:161-7.

 

Florin L, Sapp C, Streeck RE, and Sapp, M. (2002): Assembly and translocation of papillomavirus capsid proteins. J. Virol. 76: 10009-10014.

 

Schäfer F, Florin L, Sapp M. (2002): DNA binding of L1 is required for human papillomavirus morphogenesis in vivo. Virology. Sep 15;314(1):161-7.

 

Florin L, Schäfer F, Sotlar K, Streeck RE, Sapp M. (2002): Reorganization of nuclear domain 10 induced by papillomavirus capsid protein L2. Virology. Mar 30;295(1):97-107.

 

Giroglou T, Florin L, Schäfer F, Streeck RE, Sapp M. (2001): Human papillomavirus infection requires cell surface heparan sulfate. J Virol. Feb;75(3):1565-70.

 

 

 

 

 

Funding