TY - JOUR
T1 - Overlapping and independent structural roles for human papillomavirus type 16 L2 conserved cysteines
AU - Conway, Michael J.
AU - Alam, Samina
AU - Christensen, Neil D.
AU - Meyers, Craig
N1 - Funding Information:
We thank Tadahito Kanda, Kazunari Kondo, and Richard Roden for access to their anti-L2 antibodies; Horng Shen Chen and Tim Culp for assistance with qPCR; and the Meyers' laboratory for critical reading of this manuscript. This work was supported by a PHS Grant from the NIAID ( R01AI57988 ).
PY - 2009/10/25
Y1 - 2009/10/25
N2 - Cryoelectron microscopy images of HPV16 pseudovirions (PsV) depict that each pentamer of L1 can be occluded with a monomer of L2. Further research suggests that an N-terminal external loop of L2 exists, which is the target of neutralizing and cross-neutralizing antibodies. Here we show that N-terminal L2 cysteine residues, Cys22 and Cys28, have overlapping and independent structural roles, which affect both early- and late-stage assembly events. Substitution of either cysteine residue enhances infectivity markedly in comparison to wild-type HPV16. However, only Cys22Ser 20-day virions become nearly as stable as wild type. In addition, Cys22Ser, and Cys22,28Ser 20-day virions have lost their susceptibility to neutralization by anti-L2 antibodies, whereas Cys28Ser 20-day virions remain partially susceptible. These results suggest that Cys28 is necessary for late-stage stabilization of capsids, while Cys22 is necessary for proper display of L2 neutralizing epitopes.
AB - Cryoelectron microscopy images of HPV16 pseudovirions (PsV) depict that each pentamer of L1 can be occluded with a monomer of L2. Further research suggests that an N-terminal external loop of L2 exists, which is the target of neutralizing and cross-neutralizing antibodies. Here we show that N-terminal L2 cysteine residues, Cys22 and Cys28, have overlapping and independent structural roles, which affect both early- and late-stage assembly events. Substitution of either cysteine residue enhances infectivity markedly in comparison to wild-type HPV16. However, only Cys22Ser 20-day virions become nearly as stable as wild type. In addition, Cys22Ser, and Cys22,28Ser 20-day virions have lost their susceptibility to neutralization by anti-L2 antibodies, whereas Cys28Ser 20-day virions remain partially susceptible. These results suggest that Cys28 is necessary for late-stage stabilization of capsids, while Cys22 is necessary for proper display of L2 neutralizing epitopes.
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U2 - 10.1016/j.virol.2009.08.010
DO - 10.1016/j.virol.2009.08.010
M3 - Article
C2 - 19733888
AN - SCOPUS:70349840682
SN - 0042-6822
VL - 393
SP - 295
EP - 303
JO - Virology
JF - Virology
IS - 2
ER -