Papillomavirus capsid proteins mutually impact structure

Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Virology (Impact Factor: 3.32). 02/2011; 412(2):378-83. DOI: 10.1016/j.virol.2011.01.018
Source: PubMed


We studied a panel of mutant viruses containing wild-type and chimeric capsid HPV16 and HPV18 proteins. The mutant capsid protein expression, genome amplification, and episomal maintenance were comparable with the wild-type virus. However, the chimeric viruses varied in their titers from wild-type. We show that the intertypical mutant chimeric capsid viruses, that L2 affects the structure of L1 and that L1 affects the structure of L2 in the virion. These effects were measured using a panel of conformation-dependent neutralizing L1 MAbs and an L2 capsid surface peptide derived neutralizing antibody. These data suggest that variation of one capsid gene not only affects its own structure and antigenicity, but also affects the structure and antigenicity of the other capsid protein. Implications of our data suggest that for the continued effectiveness of a vaccine, variation in both capsid proteins need to be considered and not just the protein the vaccine is directed against.

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    • "Like H16.V5, based on previous immunological studies, all three antibodies were thought to recognize portions of the FG and HI loops. The H16.V5 neutralization mechanism has been shown to be one of capsid stabilization that consequently inhibits the conformational changes required during entry (Zhao et al., 2012; Rizk et al., 2008; Deschuyteneer et al., 2010; Chen et al., 2011). Although many immunological studies of H16.V5 neutralization have been published, no information on H16.V5 Fab has been recorded. "
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    ABSTRACT: Papillomaviruses (PVs) comprise a large family of viruses infecting nearly all vertebrate species, with more than 100 human PVs identified. Our previous studies showed that a mutant chimera HPV18/16 genome, consisting of the upper regulatory region and early ORFs of HPV18 and the late ORFs of HPV16, was capable of producing infectious virus in organotypic raft cultures. We were interested in determining whether the ability of this chimeric genome to produce infectious virus was the result of HPV18 and HPV16 being similarly oncogenic, anogenital types and whether more disparate PV types could also interact functionally. To test this we created a series of HPV18 chimeric genomes where the ORFs for the HPV18 capsid genes were replaced with the capsid genes of HPV45, HPV39, HPV33, HPV31, HPV11, HPV6b, HPV1a, CRPV, and BPV1. All chimeras were able to produce infectious chimeric viral particles, although with lower infectivity than wild-type HPV18. Steps in the viral life cycle and characteristics of the viral particles were examined to identify potential causes for the decrease in infectivity.
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