TY - JOUR
T1 - Interaction of L2 with β-actin directs intracellular transport of papillomavirus and infection
AU - Yang, Rongcun
AU - Yutzy IV, William H.
AU - Viscidi, Raphael P.
AU - Roden, Richard B.S.
PY - 2003/4/4
Y1 - 2003/4/4
N2 - Viruses that replicate in the nucleus, including the primary causative agent of cervical cancer, human papillomavirus type 16 (HPV16), must first cross the cytoplasm. We compared the uptake of HPV16 virus-like particles (VLPs) either with or without the minor capsid protein L2. Whereas VLPs containing only the major capsid protein L1 were diffusely distributed within the cytoplasm even 6 h post-infection, VLPs comprising both L1 and L2 exhibited a radial distribution in the cytoplasm and accumulated in the perinuclear region of BPHE-1 cells within 2 h. L2 of HPV16 or bovine papillomavirus was shown to bind to a 43-kDa cellular protein that was subsequently identified as β-actin by matrix-assisted laser desorption ionization time-of-flight analysis. A conserved domain comprising residues 25-45 of HPV16 L2 was sufficient for interaction with β-actin. HPV16 L2 residues 25-45 fused to green fluorescent protein, but not green fluorescent protein alone, colocalized with actin and caused cell retraction and disruption of the microfilament network. Finally, wild-type L2, but not L2 with residues 25-45 deleted, facilitated HPV16 pseudovirion infection. Thus, binding of β-actin by L2 residues 25-45 facilitates transport of HPV16 across the cytoplasm during infection, and blockade of this novel interaction may be useful for prophylaxis.
AB - Viruses that replicate in the nucleus, including the primary causative agent of cervical cancer, human papillomavirus type 16 (HPV16), must first cross the cytoplasm. We compared the uptake of HPV16 virus-like particles (VLPs) either with or without the minor capsid protein L2. Whereas VLPs containing only the major capsid protein L1 were diffusely distributed within the cytoplasm even 6 h post-infection, VLPs comprising both L1 and L2 exhibited a radial distribution in the cytoplasm and accumulated in the perinuclear region of BPHE-1 cells within 2 h. L2 of HPV16 or bovine papillomavirus was shown to bind to a 43-kDa cellular protein that was subsequently identified as β-actin by matrix-assisted laser desorption ionization time-of-flight analysis. A conserved domain comprising residues 25-45 of HPV16 L2 was sufficient for interaction with β-actin. HPV16 L2 residues 25-45 fused to green fluorescent protein, but not green fluorescent protein alone, colocalized with actin and caused cell retraction and disruption of the microfilament network. Finally, wild-type L2, but not L2 with residues 25-45 deleted, facilitated HPV16 pseudovirion infection. Thus, binding of β-actin by L2 residues 25-45 facilitates transport of HPV16 across the cytoplasm during infection, and blockade of this novel interaction may be useful for prophylaxis.
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U2 - 10.1074/jbc.M208691200
DO - 10.1074/jbc.M208691200
M3 - Article
C2 - 12560332
AN - SCOPUS:0038485582
SN - 0021-9258
VL - 278
SP - 12546
EP - 12553
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 14
ER -