Mutation Profile of HPV16 L1 and L2 Genes in Different Geographic Areas

Abstract

The causal relationship between HPV and cervical cancer in association with the high prevalence of high risk HPV genotypes led to the design of HPV vaccines based on the major capsid L1 protein. In recent years, capsid protein L2 has also become a focal point in the field of vaccine research. The present review focuses on the variability of HPV16 L1 and L2 genes, emphasizing the distribution of specific amino acid changes in the epitopes of capsid proteins. Moreover, a substantial bioinformatics analysis was conducted to describe the worldwide distribution of amino acid substitutions throughout HPV16 L1, L2 proteins. Five amino acid changes (T176N, N181T; EF loop), (T266A; FG loop), (T353P, T389S; HI loop) are frequently observed in the L1 hypervariable surface loops, while two amino acid substitutions (D43E, S122P) are adjacent to L2 specific epitopes. These changes have a high prevalence in certain geographic regions. The present review suggests that the extensive analysis of the amino acid substitutions in the HPV16 L1 immunodominant loops may provide insights concerning the ability of the virus in evading host immune response in certain populations. The genetic variability of the HPV16 L1 and L2 epitopes should be extensively analyzed in a given population.

Epigenetic and Genetic Keys to Fight HPV-Related Cancers

“…The L1 and L2 proteins constitute the viral capsid and are known as the major protein and minor capsid protein, respectively. They are proteins with nuclear localization signal sequences at the C-terminal end whose molecular masses of 55-60 kDa and 64-78 kDa by polyacrylamide gel electrophoresis, respectively [58][59][60]. In the late phase of the viral life cycle, they are synthesized in the cytoplasm, then imported and released into the nucleus of terminally differentiated epithelial cells via nuclear import receptors, where they assemble with the viral genome, generating new virions [58,[61][62][63].…”

“…They are proteins with nuclear localization signal sequences at the C-terminal end whose molecular masses of 55-60 kDa and 64-78 kDa by polyacrylamide gel electrophoresis, respectively [58][59][60]. In the late phase of the viral life cycle, they are synthesized in the cytoplasm, then imported and released into the nucleus of terminally differentiated epithelial cells via nuclear import receptors, where they assemble with the viral genome, generating new virions [58,[61][62][63]. Although L1 can form the capsid structure, L2 increases its stability and allows the entry phase [64] (Table 1).…”

“…It is the major HPV structural proteins that form viral capsids [58]. L2 It is the minor HPV structural proteins that form viral capsids.…”

Human Papillomavirus Requires COPI Coat Complex for a Successful Infection.

“…HPV is also responsible for a very high percentage of other anogenital cancers, and up to 70% of Head-and-Neck Cancers, which includes those of the oral cavity, oropharynx, sinus, tonsil, and larynx (40). Overall, over 600,000 new cancer cases every year are caused by high-risk HPV types, with types 16,18,31,33,35,39,45,51,52,56,58,59, and 68 being defined by WHO as cancer-causing in the cervix (41). In addition, HPV infection is the most common viral sexually transmitted infection worldwide (42).…”

Immunostaining of βA-Activin and Follistatin Is Decreased in HPV(+) Cervical Pre-Neoplastic and Neoplastic Lesions

“…The HR-HPV E6 oncoprotein generates a complex with the E3 ubiquitin ligase E6-associated protein (E6AP) to degrade p53 by polyubiquitination. However, the E7 oncoprotein, via the binding of an ordered zinc finger motif to pRb at the pRB/E2F suppressor complex, releases E2F (a transcription factor) and enables the HPV-infected cells to re-enter mitosis and proliferate [ 9 , 10 ]. In addition, some E6 spliced isoforms (E6 *) have been hypothesized to play a role in HPV-induced carcinogenesis [ 11 ].…”