Conserved Features in Papillomavirus and Polyomavirus Capsids

Abstract

Capsids of papilloma and polyoma viruses (papovavirus family) are composed of 72 pentameric capsomeres arranged on a skewed icosahedral lattice (triangulation number of seven, T = 7). Cottontail rabbit papillo mavirus (CRPV) was reported previously to be a T = 7laevo (left-handed) structure, whereas human wart virus, simian virus 40, and murine polyomavirus were shown to be T = 7dextro (right-handed). The CRPV structure determined by cryoelectron microscopy and image reconstruction was similar to previously determined structures of bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 1 (HPV-1). CRPV capsids were observed in closed (compact) and open (swollen) forms. Both forms have star-shaped capsomeres, as do BPV-1 and HPV-1, but the open CRPV capsids are ~2 nm larger in radius. The lattice hands of all papillomaviruses examined in this study were found to be T = 7dextro. In the region of maximum contact, papillomavirus capsomeres interact in a manner similar to that found in polyomaviruses. Although papilloma and polyoma viruses have differences in capsid size (~60 versus ~50 nm), capsomere morphology (11 to 12 nm star-shaped versus 8 nm barrel-shaped), and intercapsomere interactions (slightly different contacts between capsomeres), papovavirus capsids have a conserved, 72-pentamer, T = 7dextro structure. These features are conserved despite significant differences in amino acid sequences of the major capsid proteins. The conserved features may be a consequence of stable contacts that occur within capsomeres and flexible links that form among capsomeres.

A thermally induced phase transition in a viral capsid transforms the hexamers, leaving the pentamers unchanged

“…Examples include the 120-subunit capsids of double-stranded RNA viruses (e.g. (Butcher et al, 1997;Cheng et al, 1994;Grimes et al, 1998); the 360-subunit, all-pentamer, capsids of papillomaviruses and polyomaviruses (Belnap et al, 1996); and the icosahedrally ordered envelopes of flaviviruses such as dengue (Kuhn et al, 2002).…”

Replication and Assembly of Human Papillomaviruses

“…3). Generally, expression plasmids or viral vectors that express L1 alone, or L1 plus L2, are transfected or used to infect the following eukaryotic or prokaryotic cell types: 293T, BSC-1, E. coli, yeast, or Sf9 cells (Kirnbauer et al, 1992(Kirnbauer et al, , 1993Hagensee et al, 1993Hagensee et al, , 1994Rose et al, 1993;Belnap et al, 1996;Zhang et al, 1998;Chen et al, 2000;Querbes et al, 2006). Upon expression of L1, structures which retain the native T=7 icosahedral symmetry of the native virions are intracellularly self-assembled.…”

“…VLPs are antigenically similar to native virions, suggesting gross structural similarities. In fact, VLPs can induce high titers of type-specific neutralizing antibodies, which made them good candidates for first-generation HPV vaccines (Rose et al, 1994;Belnap et al, 1996;Harper et al, 2004). While not necessary for the production of VLPs, one advance in VLP technology incorporates L2 into the particle, which has been suggested to increase their overall stability Gambhira et al, 2007;Kondo et al, 2007).…”

“…Initial infection by HPVs is thought to occur through micro-abrasions of the epithelial tissue, thus allowing entry of the HPV particle into cells of the basal layer (Belnap et al, 1996). Basal layer cells consist mainly of stem cells and transit-amplifying cells, and it is the epithelial stem cells that must be infected for a lesion to be maintained (Kaur and Li, 2000;Egawa, 2003).…”

The Viral Etiology of AIDS‐Associated Malignancies

“…Disulfide bond interactions between L1 molecules are important in particle assembly and disassembly . There are 12 L2 minor capsid proteins that are associated with the inner surface of the L1 pentamers (Belnap et al, 1996). High resolution cryoelectron microscopic structures of bovine papillomavirus (BPV) have been achieved (Baker et al, 1991); less is known about HPV structure, assembly, and uncoating.…”