Anti-HPV16 L1 polyclonal antibody

HPVs, or Human Papillomaviruses, stand as the predominant culprits behind sexually transmitted viral infections in humans. Specifically, contracting high-risk HPVs, such as HPV16, significantly heightens the risk of cervical cancer. The papillomavirus L1 major capsid protein, the basis of the currently marketed vaccines, self-assembles into virus-like particles (VLPs). The HPV capsid is composed of two structural proteins, L1 and L2,synthesized late in the infectious cycle. These two proteins encapsidate a histone-associated, closed circular, double-stranded DNA minichromo some. The outer shell of the virion contains 72 pentamers of L1, centered on the vertices of a T=7 icosahedral lattice. L2, a largely internal protein, is present at about 1/30 the abundance of L1. The papillomavirus major capsid protein L1 is intrinsically able to self-assemble into virus-like particles. These particles are morphologically indistinguishable from native virions and present the conformational epitopes necessary for the induction of high titers of neutralizing antibodies.

Researchers have expressed the HPV16 L1 protein in E. coli and determined its crystal structure at 3.5 A ˚ resolution. The crystallization conditions favor formation of a 12-pentamer, T=1 icosahedral assembly of L1, which they describe as a "small VLP." Assembly experiments in vitro show that a short, N-terminal segment of the L1 polypeptide chain acts as a switch between 72-pentamer, virion-like assemblies and small VLPs. The L1 subunit shave similar folded structures as their polyoma VP1 counterparts, but the modes of interpentamer association in polyoma virions and papilloma small VLPs are quite distinct. The L1structure can be used to direct engineering of chimeric VLP vaccines, locate dominant neutralizing epitopes, identify mechanisms of neutralization by antibodies, and rationalize differences among viral serotypes.

Figure 1. HPV16 L1 Monomer and Pentamer, with Polyomavirus VP1 Monomer for Comparison.
(Source: Molecular Cell. 2000.)

L1 monomer, viewed roughly normal to the five-fold axis of a pentamer. The structure includes residues 20–474; the first and last residues are labeled N(20) and C(474), respectively. Polyomavirus VP1 monomer, viewed in essentially the same direction as the L1 monomer in (A). Blue, pink, red, and green have the same significance as in the representation of L1; a C-terminal arm, "invading" from another pentamer (triple-primed letters), is yellow; the proximal part of the arm of the monomer in the figure, which extends into the neighboring pentamer, is light yellow; distalparts of this arm are not shown. L1 pentamer, viewed normal to the five-fold axis. The C-terminal projection of the central (blue) monomer is shown in yellow. L1 pentamer, viewed along the five-fold axis from outside the particle. As in (C), the C-terminal projection of the blue monomer is yellow.