The tetraspanin CD151 in papillomavirus infection - PubMed (original) (raw)

Review

The tetraspanin CD151 in papillomavirus infection

Konstanze D Scheffer et al. Viruses. 2014.

Abstract

Human papillomaviruses (HPV) are non-enveloped DNA tumor viruses that infect skin and mucosa. The most oncogenic subtype, HPV16, causes various types of cancer, including cervical, anal, and head and neck cancers. During the multistep process of infection, numerous host proteins are required for the delivery of virus genetic information into the nucleus of target cells. Over the last two decades, many host-cell proteins such as heparan sulfate proteoglycans, integrins, growth factor receptors, actin and the tetraspanin CD151 have been described to be involved in the process of infectious entry of HPV16. Tetraspanins have the ability to organize membrane microdomains and to directly influence the function of associated molecules, including binding of receptors to their ligands, receptor oligomerization and signal transduction. Here, we summarize the current knowledge on CD151, and CD151-associated partners during HPV infection and discuss the underlying mechanisms.

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Figures

Figure 1

Schematic diagram showing published tetraspanin partners. Proteins essential for HPV16 infection are shown in black [22,23,24,28,29,30,31,32,33,36,37,38,39,40,41,42].

Figure 2

HPV16 infection: (A) Cell surface events. Virus particles bind to heparan sulfate proteoglycans (HSPGs) and non-HSPG proteins (laminin-332, growth factors) inducing activation of growth factor receptors and integrins. After conformational changes of both capsid proteins by HSPG binding, cyclophilin B, and furin, papillomavirus particles become transferred to the second receptor complex (CD151, CD63, annexin A2, laminin, α6-integrin, growth factors, and their receptors) in tetraspanin enriched microdomains. The tetraspanin CD151 and actin mediate a clathrin-, caveolin-, and dynamin-independent endocytosis of the virus probably by membrane budding and vesicle scission. (B) Virus binding and uptake leads to virus accumulation in CD63 positive endosomes. Acidification and cyclophilin B enable capsid disassembly and uncoating of the infectious complex (L2/vDNA). L2-mediated trafficking leads to accumulation of the L2/vDNA complex at PML nuclear bodies. The differentiation program of infected keratinocytes controls virus transcription and replication. Finally, new HPV particles are assembled in the host-cell nucleus.

Figure 3

Schematic view of tetraspanin CD151 with four transmembrane domains (TM1‑4), two extracellular domains (EC1, EC2) with helices A–E, and three disulfide bonds (dashed lines). Some amino acids were represented in one-letter code. Residues important for HPV16 endocytosis are shown in black: The juxtamembrane cysteines that constitute potential palmitoylation sites, the N-glycosylation site, the QRD-motif required for integrin interaction and the C-terminus of the CD151 molecule.

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The tetraspanin CD151 in papillomavirus infection - PubMed (original) (raw)