Human papillomavirus genome variants

Burk, Robert D.; Harari, Ariana; Chen, Zigui

doi:10.1016/j.virol.2013.07.018

Cited by 407 publications

(536 citation statements)

References 87 publications

(155 reference statements)

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“…On the other hand, the topologies of the trees constructed with each of the nine individual ORFs and the URR were dichotomous, clearly identifying lineages A and B but poorly resolving sublineages A1 to A4. These observations further support the established concept of complete genome sequencing for the basis of HPV variant classification (42,46). Because nucleotide changes specific to genetic (sub)lineages are not evenly dispersed throughout the HPV genome, the generation of phylogenetic trees with sequences from individual genomic regions may result in trees with different topologies.…”

Section: Discussionsupporting

confidence: 65%

“…Overall, 64/78 (82.1%) of the complete HPV11 genome sequences determined to date were identified by members of our international HPV11 consortium. Nucleotide sequence differences across the complete HPV genome of 1.0% to 10.0% and 0.5% to 1.0% define distinct HPV variant lineages and sublineages, respectively (26,42). In this study, the calculated maximal pairwise difference between nucleotide sequences among the 78 complete HPV11 genomes analyzed was 1.3%, indicating the existence of two HPV11 variant lineages.…”

Section: Discussionmentioning

confidence: 59%

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Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

Jelen

Chen

Kocjan

et al. 2016

J Virol

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Human papillomavirus 11 (HPV11) is an etiological agent of anogenital warts and laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic HPV vaccines. We established the largest collection of globally circulating HPV11 isolates to date and examined the genomic diversity of 433 isolates and 78 complete genomes (CGs) from six continents. The genomic variation within the 2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207 (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11 variants containing unique single nucleotide polymorphisms (SNPs), indels (insertions or deletions), or amino acid changes were fully sequenced. A maximum likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific SNPs within the CG were identified, as well as the 208-bp representative region for CG-based phylogenetic clustering within the partial E2 open reading frame and noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by sublineages A1, A3, and A4 and lineage B. IMPORTANCEThis collaborative international study defined the global heterogeneity of HPV11 and established the largest collection of globally circulating HPV11 genomic variants to date. Thirty novel complete HPV11 genomes were determined and submitted to the available sequence repositories. Global phylogenetic analysis revealed two HPV11 variant lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the representative region identified within the partial genomic region E2/noncoding region 2 (NCR2) will enable the simpler identification and comparison of HPV11 variants worldwide. This study provides an important knowledge base for HPV11 for future studies in HPV epidemiology, evolution, pathogenicity, prevention, and molecular assay development. Human papillomavirus 11 (HPV11), which belongs to species 10 of the Alphapapillomavirus genus (Alpha-PV), is etiologically associated with approximately 20% of anogenital warts and 30 to 40% of laryngeal papillomas (1-11). HPV11 is generally considered a low-risk HPV type due to its rare presence in HPVrelated cancers in humans, especially cervical cancer (9). HPV11 is present in 0.5% of samples from HPV-positive women with a normal cytology worldwide and causes 2.3% of cervical low-grade squamous cell intraepithelial lesions (12, 13). However, rare case reports of HPV11-positive cases of cervical and anal squamous cell carcinomas, malignantly transformed laryngeal papillomas, and sinonasal inverted papillomas associated with squamous cell carcinoma can be found in the literature (14-21). Due to its clinical significance, HPV11 has been included in the current quadrivalent and nonavalent prophylactic HPV vaccines (22,23).The genetic diversity of HPV11 was studied for the first time in 1995, when Heinzel et al. sequenced the noncoding upstre...

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 59%

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

Jelen

Chen

Kocjan

et al. 2016

J Virol

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“…The sequences determined were aligned with available sequences from the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/) database including the HPV51 reference (GenBank accession no. M62877) and an isolate from Japan (GQ487711 and GQ487712) (Kondo et al, 2009 (Burk et al, 2013). Alignments and neighbour-joining tree reconstruction (500 iterations) were carried out using MEGA6 (Tamura et al, 2013).…”

mentioning

confidence: 99%

“…The remaining sequences (5/34; 15 %) clustered adjacent to, but in some cases distinct from, sequences representing sublineages A2, A3, A4, B1 and B2. It is unclear at this time whether sequences that do not segregate into these sublineages are due to a lack of sufficient diagnostic motifs in the L1 and L2 genes, compared with the full genome sequences from which they were derived (Burk et al, 2013), or whether additional sublineages exist.…”

mentioning

confidence: 99%

Amino acid motifs in both the major and minor capsid proteins of HPV51 impact antigenicity and infectivity

Godi

Epifano

Bissett

et al. 2015

Journal of General Virology

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Persistent infection with oncogenic human papillomavirus (HPV) is a prerequisite for cervical disease development, yet data regarding the host immune response to infection at the genotype level are quite limited. We created pseudoviruses bearing the major (L1) and minor (L2) capsid proteins and L1 virus-like particles representing the reference sequence and a consensus of 34 European sequences of HPV51. Despite the formation of similarly sized particles, motifs in the reference L1 and L2 genes had a profound impact on the immunogenicity, antigenicity and infectivity of these antigens. The antibody status of women exhibiting low-grade disease was similar between HPV16 and the consensus HPV51, but both demonstrated discrepancies between binding and neutralizing antibody responses. These data support the use of pseudoviruses as the preferred target antigen in studies of natural HPV infection and the need to consider variation in both the L1 and L2 proteins for the appropriate presentation of antibody epitopes. Received 5 November 2014 Accepted 12 March 2015Persistent infection with one or more of about a dozen human papillomavirus (HPV) genotypes (Bouvard et al., 2009) is associated with the development of cervical cancer, a significant cause of morbidity and mortality in women worldwide (Schiffman et al., 2007). The propensity for certain genotypes to persist longer than others (Rositch et al., 2013) may contribute to the observed HPV genotype distribution differences between low-grade disease and cervical cancer (Guan et al., 2012).The non-enveloped capsid of HPV comprises the major (L1) and minor (L2) capsid proteins. The L1 protein facilitates virus attachment to host cells, whilst the L2 protein is essential for subsequent virus infectivity (Buck et al., 2013;Raff et al., 2013;Wang & Roden, 2013).Current L1 virus-like particle (VLP)-based HPV vaccines target the most prevalent genotypes, HPV16 and HPV18, and elicit type-specific neutralizing antibodies thought to confer the high levels of efficacy observed in clinical trials (Lehtinen & Dillner, 2013;Schiller et al., 2012). A limited number of serological assays are available for measuring vaccine type-specific antibody responses, including an L1 VLP ELISA, a mAb competitive VLP assay and an L1L2 pseudovirus neutralization assay. Despite some discrepancies, overall inter-assay agreements are good (Dessy et al., 2008;Krajden et al., 2014). Natural infection (NI) studies usually compare the HPV DNA status of individuals with their respective antibody status in order to better understand the pathogen-host relationship. Most of these studies have examined HPV16 and/or HPV18 (Castellsagué et al., 2014;Lin et al., 2013;Pastrana et al., 2004; Safaeian et al., 2010;Xi et al., 2002), whilst some have expanded their investigations to evaluate other genotypes including HPV6, HPV11, HPV31, HPV33, HPV35, HPV45, HPV52 and HPV58 (Carter et al., 2000;Ochi et al., 2008; Syrjänen et al., 2009;Wilson et al., 2013). Most of these studies have made use of an immobilized L1-based t...

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“…[2][3][4][5] So that, Because of the risk of oncogenic, it was utilized as a type of mutant protein with three substitution in amino acids. Therefore called E7 detox (E7d).…”

Section: Introductionmentioning

confidence: 99%

HPV16E7d Candidate Vaccine Modified Genes Expression in Tumor Environment: Flic as Adjuvant Changed TGF-B Gene Expression

Mahdavi

Rakhshani

Riazi-Rad

2017

ACP

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Cervical cancer is one of the most important venereal disease and leads to mortality in women. Human papilloma virus causes this disease. This virus has three protein zones that includes of Early, Late and None coding areas. The early phase consists of E1 to E7 but E6 and E7 are two early oncoproteins of HPV which are responsible for disordering in cell cycle and tumor induction. In this study, the efficiency of FlicE7d-HPV16 and HPV16-E7d-Flic were investigated in tumor bearing Mice models .Tumor was induced in mice with transplantation method. After tumor growth, the mice were divided into five groups. two groups of C57BL/6 Mice were injected with 20µg of the vaccine Flic-E7d-HPV16 and E7d-HPV16-Flic subcutaneously three times with one week interval. The third group only E7d was injected and for fourth group only Flic was injected and for fifth group PBS was injected. One week after final immunization, tumor was assessed for gene expression and pathologic smear. According to pathological studies on the tumor samples of mice which indicated the tumor was kind of Sarcoma, Necrosis, Apoptosis, Mitosis and vessel generation were evaluated in each group. Apoptosis and angiogenesis in A, B group were not observed. According to investigation of TGF-β and VEGF genes and HPRT control gene using PCR-real-Time, there was a decrease of VEGF and TGF-β genes in group A and B. SO the vaccine of group A, B were potent in the reduction of angiogenesis. As a result, Flic as an adjuvant improved anti-tumor effect of HPV16 E7d vaccine.

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Human papillomavirus genome variants

Cited by 407 publications

References 87 publications

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

Amino acid motifs in both the major and minor capsid proteins of HPV51 impact antigenicity and infectivity

HPV16E7d Candidate Vaccine Modified Genes Expression in Tumor Environment: Flic as Adjuvant Changed TGF-B Gene Expression

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