Naturally occurring capsid protein variants L1 of human papillomavirus genotype 16 in Morocco

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.

Genetic diversity and phylogenetic analysis of HPV 16 & 18 variants isolated from cervical specimens of women in Saudi Arabia

“…Human papillomavirus (HPV) is a circular dsDNA virus belongs to the family Papillomaviridae . The viral genome size range from ∼7.9–8.0 kb in length containing six early genes (E1, E2, E4, E5, E6 and E7) and 2 late genes designated as L1, L2 (Doorbar et al, 2012, Van Doorslaer et al, 2013, El-Aliani et al, 2017, Van der Weele et al, 2018). Currently, approximately 200 HPVs genotypes have been identified and divided based on more than 10% nucleotide diversity of L1 gene (Van Doorslaer et al, 2013, Ervik et al, 2016, Basto et al, 2017, Islam et al, 2018).…”

“…A prophylactic vaccine known as AS04-adjuvanted HPV16/18 vaccine designated as Cervarix® has been developed by GlaxoSmithKline Biologicals, Belgium, consisting of virus-like particles derivatives of HPV16 and 18 L1 proteins (McKeage and Romanowski, 2011, Zhu et al, 2017). Based on previous studies, the genetic variation in L1 gene significantly affects the viral assembly, protein structure/confirmation results into altered biological functions and host immunogenic recognition with clinical significance (El-Aliani et al, 2017). The information about genetic diversity of HPV16 and HPV18 genotypes have been published in many reports worldwide (Shen et al, 2013, Assoumou et al, 2015, King et al, 2016, Nicolas-Parraga et al, 2016, Doorslaer et al, 2017, Islam et al, 2018, Van der Weele et al, 2018, Liu et al, 2018, Xu et al, 2018, Aziz et al, 2018, Tao et al, 2018, Ramas et al, 2018, Yoon et al, 2018).…”

Abundance of HPV L1 Intra-Genotype Variants With Capsid Epitopic Modifications Found Within Low- and High-Grade Pap Smears With Potential Implications for Vaccinology

“…However, functional consequences of these mutations were not studied. Another investigation found multiple mutations within the L1 fragment of HPV-16 (MY09/11-primed amplicons) of 35 invasive cervical cancer samples from Morocco (El-Aliani et al, 2017). A distinct mutation in the HI loop (T389P) found in 51.4% of cases could potentially interact with vaccine-induced neutralizing antibodies (El-Aliani et al, 2017).…”

“…Another investigation found multiple mutations within the L1 fragment of HPV-16 (MY09/11-primed amplicons) of 35 invasive cervical cancer samples from Morocco (El-Aliani et al, 2017). A distinct mutation in the HI loop (T389P) found in 51.4% of cases could potentially interact with vaccine-induced neutralizing antibodies (El-Aliani et al, 2017). In view of this information, our results are highly consistent with the findings of high intra-host and intra-type L1 sequence variability that could potentially impact vaccine efficacy.…”

“…These remarkable findings of L1 genetic variability are clinically important due to potential structural changes on the epitopes of virions arising from nonsynonymous mutations. The result may be ineffectual binding by host neutralizing antibodies induced by either natural infections or prophylactic vaccines (Bissett et al, 2016; El-Aliani et al, 2017).…”