|
Basic Characteristics of Mutations
|
|
Mutation Site
|
C428G |
|
Mutation Site Sentence
|
This paper analyses, using a panel of well-characterised Mabs, the effects on the antigenicity of various C- and N-terminal deletants of HPV-16 L1 made in insect cells via recombinant baculovirus, of an A-->T mutation at residue 266 (A266T), and of a C-->G mutation at conserved position 428 (C428G). |
|
Mutation Level
|
Nucleotide level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
L1 |
|
Standardized Encoding Gene
|
L1
|
T mutation at residue 266 (A266T), and of a C-->G mutation at conserved position 428 (C428G).
-->
|
Genotype/Subtype
|
HPV16 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Papillomavirus Infections
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
16938363
|
|
Title
|
A deletion and point mutation study of the human papillomavirus type 16 major capsid gene
|
|
Author
|
Varsani A,Williamson AL,Jaffer MA,Rybicki EP
|
|
Journal
|
Virus research
|
|
Journal Info
|
2006 Dec;122(1-2):154-63
|
|
Abstract
|
Recombinant human papillomavirus (HPV) virus-like particles (VLPs) made from the major capsid protein L1 are promising vaccine candidates for use as vaccines against genital and other HPV infections, and particularly against HPV-16. However, HPV-16 genotype variants have different binding affinities for neutralising mouse Mabs raised against HPV-16 L1 VLPs. This paper analyses, using a panel of well-characterised Mabs, the effects on the antigenicity of various C- and N-terminal deletants of HPV-16 L1 made in insect cells via recombinant baculovirus, of an A-->T mutation at residue 266 (A266T), and of a C-->G mutation at conserved position 428 (C428G). The effects of these changes on assembly of the variant L1s were studied by electron microscopy. Binding of Mab H16:E70 to A266T was reduced by almost half in comparison to wild type L1. Retention of the C-terminal region 428-483 was critical for the binding of conformation-specific Mabs (H16:V5, H16:E70, H16:U4 and H16:9A) whereas deletion of the nuclear localisation signal (NLS) or the C428G mutation or an N-terminal deletion (residues 2-9) did not affect the antigenicity. The N-terminal deletion resulted in a mixed population of 30 and 55nm VLPs, which differs from the same construct expressed in Escherichia coli, whereas pentamer aggregates resulted from deletion of the 428-465 region or the C428G mutation. The results have implications both for considering use of single-genotype HPV vaccines, and for design of novel second-generation vaccines.
|
|
Sequence Data
|
-
|
|
|