Abstract
HPV L1 protein is a corner stone in HPV structure, it's involved in the formation of the viral capsid; widely used as a systematic material and considered as the main component in vaccines development and production. The present study aims to characterize genetic variation of L1 gene of HPV 16 specimens and to evaluate in silico the impact of major variants on the epitope change affecting its conformational structure. A fragment of L1 gene from 35 HPV 16 confirmed specimens were amplified by PCR and sequenced. Overall, five amino acids residues changes were reported: T390P in 16 specimens, M425I and M431I in 2 cases, insertion of Serine at 460 and aspartic acid deletion at position 477 in all analyzed cases. The 3D generated model showed that T389P amino acid substitution is located in the H-I loop; the two substitutions M424I and M430I are both located in the H2 helice. The Serine insertion and aspartic acid deletion are located in the H4 helice and B-C loop, respectively. Superimposition of sequences' structures showed that they share a very similar conformation highlighting that the reported amino acids variations don't affect the structure of the L1 protein. However T389P, located in the H-I loop identified as an immunogenetic region of L1 capsid, was reported in 51.4% of cases could interact with vaccines induced monoclonal antibodies suggesting a potential impact on the efficacy of available anti-HPV vaccines.
Highlights
Worldwide, Cervical cancer is the fourth most common cancer in women, with an estimated 528,000 new cases in 2012, and more than 85% of the global burden occurs in developing countries, where it accounts for 13% of all female cancer [1]
Human papillomavirus (HPV) genomes are circular dsDNA characterized by eight open reading frames (ORFs), which are all transcribed from the same DNA strand and orientation, and yield two classes of proteins which are classified as non-structural regulatory proteins (E1-E7) and structural proteins L1 and L2 based on their temporal expression
The intrinsic capacity of L1 proteins to assemble into empty capsid-like structures has been used to develop virus like particles (VLPs) largely used in the induction of protective immunity in animal models [5] and the development of prophylactic vaccines for HPV infection [6,7,8]
Summary
Cervical cancer is the fourth most common cancer in women, with an estimated 528,000 new cases in 2012, and more than 85% of the global burden occurs in developing countries, where it accounts for 13% of all female cancer [1]. There’s evidence that persistent infection with high risk Human papillomavirus (HPV) is the main etiological factor in the development of cervical cancer [2]. Of these high-risk types, HPV-16 and HPV-18 are responsible for about 70% of cervical cancers [3]. The intrinsic capacity of L1 proteins to assemble into empty capsid-like structures has been used to develop virus like particles (VLPs) largely used in the induction of protective immunity in animal models [5] and the development of prophylactic vaccines for HPV infection [6,7,8]. Two prophylactic vaccines; Cervarix (GSK) and Gardasil (Merck); based on the L1 proteins of HPV16 and HPV18, have been introduced into the immunization schedule in many developed and some developing countries [9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
