New HPV-16 European and non-European variants in Central Brazil

Abstract

HPV-16 is the most prevalent human papillomavirus genotype found in cervical intraepithelial neoplasias. The regulatory region of the HPV genome, LCR, has several binding sites for cellular and viral transcription factors, and nucleotide substitutions in this genomic region can interfere with the viral oncogenic expression. The present study aims to determine the LCR variability of European and non-European HPV-16 variants found in Brazil. Through automated sequencing, it was possible to characterize the LCR of ten non-European (eight Asian-American, one African 1, one African 2) and twelve European isolates. Among the 22 isolates analyzed, nine may be new variants of HPV-16, with different combinations of previously reported nucleotide substitutions, and three showed new substitutions not previously reported. Two new nucleotide substitutions, the insertion of T at position 7621 and the substitution of A to G at position 7836, were found in a single isolate, Bsb-14, a putative new African 1 variant. The characterization of the LCR of human papillomaviruses can be of pivotal importance to the understanding of the viral replication and pathogenicity.

Prevalence of human papillomavirus (HPV) type 16 variants and rare HPV types in the central Amazon region

“…This was also found in southeastern (Villa et al, 2000) and central Brazil (Cruz et al, 2004;Alencar et al, 2007). Variants of HPV type 16 are typically classified into European, African, Asian-American, and North-American, or Amerindian (Yamada et al, 1997).…”

“…Cervical cancer is the most common disease in Brazilian women, and infection by HPV is the main risk factor for development of this pathology. In Brazil, most studies of HPV were conducted in southeastern (Villa et al, 2000) or in central regions of the country (Cruz et al, 2004;Alencar et al, 2007;Cerqueira et al, 2008).…”

Entire genome characterization of human papillomavirus type 16 from infected Thai women with different cytological findings

“…HPV16 variants coevolved with the three major phylogenetic ethnic groups-Africans, Caucasians, and Asians. These variants clustered into five distinct groups: European (E), Asian (As), Asian-American (AA) which originated from Central and South America, African 1 (Af-1), and African 2 (Af-2) [14,15] and some authors have suggested that certain HPV-16 non-European variants are associated with a higher risk of cervical intraepithelial neoplasia and invasive cancer [16]. In a critical genome region of the HPV 16 variant such as the long control region (LCR), the E6 and the E2 genes may be associated with the oncogenic potential of HPV [17,18].…”

“…In a critical genome region of the HPV 16 variant such as the long control region (LCR), the E6 and the E2 genes may be associated with the oncogenic potential of HPV [17,18]. Molecular characterization of the variability found in the LCR may contribute to better understand the association of HPV16, especially the nonEuropean variants, with a potentially greater oncogenicity [16]. Some previous reports have studied HPV16 at different stages of cervical cancer by examining the distribution of the LCR, E7, E6, L1, L2, and E2 polymorphisms [19][20][21][22][23][24].…”

Upstream Regulatory Region Alterations Found in Human Papillomavirus Type 16 (HPV-16) Isolates from Cervical Carcinomas Increase Transcription, ori Function, and HPV Immortalization Capacity in Culture

“…Numerous variants of the prototypical HPV-16 URR sequence (17) have been described (1,10,36,66,67); similar sequence variation has been observed in other HR and low-risk HPV types (2,8,9,26,42,45). Some of the nucleotide changes exhibit characteristic geographic distributions and have been grouped into evolutionary variants: the European (E), North American 1 (NA1), and Asian-American (AA) variants.…”