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PMID:23302890

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Citation

Scheffer, KD, Gawlitza, A, Spoden, GA, Zhang, XA, Lambert, C, Berditchevski, F and Florin, L (2013) Tetraspanin CD151 mediates papillomavirus type 16 endocytosis. J. Virol. 87:3435-46

Abstract

Human papillomavirus type 16 (HPV16) is the primary etiologic agent for cervical cancer. The infectious entry of HPV16 into cells occurs via a so-far poorly characterized clathrin- and caveolin-independent endocytic pathway, which involves tetraspanin proteins and actin. In this study, we investigated the specific role of the tetraspanin CD151 in the early steps of HPV16 infection. We show that surface-bound HPV16 moves together with CD151 within the plane of the membrane before they cointernalize into endosomes. Depletion of endogenous CD151 did not affect binding of viral particles to cells but resulted in reduction of HPV16 endocytosis. HPV16 uptake is dependent on the C-terminal cytoplasmic region of CD151 but does not require its tyrosine-based sorting motif. Reexpression of the wild-type CD151 but not mutants affecting integrin functions restored virus internalization in CD151-depleted cells. Accordingly, short interfering RNA (siRNA) gene knockdown experiments confirmed that CD151-associated integrins (i.e., α3β1 and α6β1/4) are involved in HPV16 infection. Furthermore, palmitoylation-deficient CD151 did not support HPV16 cell entry. These data show that complex formation of CD151 with laminin-binding integrins and integration of the complex into tetraspanin-enriched microdomains are critical for HPV16 endocytosis.

Links

PubMed PMC3592167 Online version:10.1128/JVI.02906-12

Keywords

Antigens, CD151/genetics; Antigens, CD151/metabolism; Cell Line; DNA Mutational Analysis; Endocytosis; Gene Knockdown Techniques; Human papillomavirus 16/physiology; Humans; Mutant Proteins/genetics; Mutant Proteins/metabolism; Virus Internalization

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CD151

GO:0005604: basement membrane

ECO:0000314:

C

Figure 1 shows the distribution of CD151 in the basement membrane of human cervical mucosa through staining.

complete
CACAO 10034

HUMAN:CD151

part_of

GO:0005604: basement membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

See also

References

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