Human papillomavirus (HPV) is a DNA virus from the papillomavirus family that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes. L1 is a major capsid protein of human papilloma virus. Infection with specific types of HPV has been associated with an increased risk of developing cervical neoplasia. Does not bind DNA.
Keywords
HPV 58 L1; L1; Major capsid protein L1
Citations
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Background
Human papillomavirus (HPV) is associated with 99% of cervical cancers, and persistent HPV infection leads to the development of cervical cancer, with different high-risk HPV types showing geographic/ethnic variability, with HPV 58 ranking as the sixth or seventh most common cause of cervical cancer globally, but the third most common HPV type in East Asia. HPV 58 is found in 10% to 18% of cervical cancers in East Asia, but is rare elsewhere. The definition of HPV type is that the sequence difference of L1 genome is more than 10%, while the difference of variant pedigree and subline in complete genome is 1% to 10% and 0.5% to 1%, respectively. Great differences in evolutionary correlation and carcinogenicity were observed at the level of type and variation. In a multi-continental epidemiological study, HPV 58E7T20I/G63S variants are more commonly detected in East Asia, and the risk of cervical cancer is 7 to 9 times higher than in other regions, indicating that the virus mutation plays a key role in regulating its unique carcinogenic characteristics. These data strongly suggest that sequence variations at certain sites in the HPV genome can critically determine phenotypic characteristics, including carcinogenicity. The nine-valent vaccine currently available on the market covers a wide range of HPV types, including HPV 58, which can prevent 90% of cervical cancer infections from HPV types.
The HPV major capsid protein L1 has some very conserved regions that can be used for the design and development of vaccines against human papillomavirus infection due to their specific conformational epitopes and their ability to self-assemble into virus-like particles (VLPs). L1-VLP is an empty capsid produced by self-assembly of the pentamer of the major capsid protein L1, which has the same morphology and antigenicity as natural viral particles but does not contain viral DNA or oncogenic proteins. It is safe, highly immunogenic, provides the immune system with conformational epitopes identical to those of naturally occurring infectious viruses, induces both innate and acquired immune responses and produces high titers of virus-neutralizing antibodies. 22 non-synonymous mutations were found in the major capsid protein L1 of HPV 58. However, the function of these mutations and their effects on the conformational structure of epitopes and their binding affinity to monoclonal antibodies need to be further studied.
Figure 1. Geographic distribution of HPV 58 variants (Source: Chen Z, et al. 2017)
Alternative Names
Human papillomavirus type 58 L1 protein Human papillomavirus 58 L1 protein HPV 58 L1 HPV 58 major capsid protein L1
References
1. Chen Z, et al. Ancient Evolution and Dispersion of Human Papillomavirus 58 Variants. J Virol. 2017 Oct 13;91(21):e01285-17.
2. Oumeslakht L, et al. Worldwide genetic variations in high-risk human papillomaviruses capsid L1 gene and their impact on vaccine efficiency. Gene. 2021 May 25;782:145533.
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References
HPV58 E7 Protein Expression Profile in Cervical Cancer and CIN with Immunohistochemistry
J Cancer
Authors: Zheng Q, Chen X, Han R, Zhu J, Wang H, Chen L, Song Y, Chen L, Cheng H, Jin N.
Background: The persistent infection of high-risk human papillomavirus (HR-HPV) is one of the most common causes of cervical cancer worldwide, and HPV type 58 (HPV58) is the third most common HPV type in eastern Asia. The E7 oncoprotein is constitutively expressed in HPV58-associated cervical cancer cells and plays a key role during tumorigenesis. This study aimed to assess the HPV58 E7 protein expression in the tissues of cervical cancer and cervical intraepithelial neoplasia (CIN). Methods: A total of 67 HPV58-positive cervical samples were collected, including 25 cervical cancer samples and 42 CIN samples. All the tissues were examined by HPV58 E7, p16INK4a and Ki67 immunohistochemistry (IHC). At last, we analyzed their association with clinical and pathological variables. Results: HPV58 E7 expression was detected in 96% of the HPV58 DNA-positive cervical cancer tissues and 85.7% of HPV58-positive CIN tissues. 65 samples of cervical cancer and CIN tissues had p16-positive staining, while 59 samples were Ki-67 positive. Conclusions: HPV58 E7 protein is highly expressed in both cervical cancer and CIN tissues. HPV58 E7 IHC could be sensitive and specific for evaluating HPV-driven cervical cancer and pre-cancerous lesions, in combination with p16 and Ki-67 IHC.
E7 Oncogene HPV58 Variants Detected in Northeast Brazil: Genetic and Functional Analysis
Cervical cancer is associated with persistent infections by high-risk Human Papillomavirus (HPV) types that may have nucleotide polymorphisms and, consequently, different oncogenic potentials. Therefore, this study aimed to evaluate the genetic variability and structural effects of the E7 oncogene of HPV58 in cervical scraping samples from Brazilian women. The study was developed with patients from hospitals in the metropolitan area of Recife, PE, Brazil. The most frequent HPV types were, in descending order of abundance, HPV16, 31, and 58. Phylogenetic analysis demonstrated that the isolates were classified into sublineages A2, C1, and D2. Two positively selected mutations were found in E7: 63G and 64T. The mutations G41R, G63D, and T64A in the E7 protein reduced the stability of the protein structure. Utilizing an NF-kB reporter assay, we observed a decrease in the NK-kB pathway activity with the HPV58-E7 variant 54S compared to the WT E7. The other detected E7 HPV58 variants presented similar NF-kB pathway activity compared to the WT E7. In this study, it was possible to identify mutations that may interfere with the molecular interaction between the viral oncoproteins and host proteins.