Epidemiological and functional implications of molecular variants of human papillomavirus

Abstract

Human papillomavirus genomes are classified into molecular variants when they present more than 98% of similarity to the prototype sequence within the L1 gene. Comparative nucleotide sequence analyses of these viruses have elucidated some features of their phylogenetic relationship. In addition, human papillomavirus intratype variability has also been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Until the present, little has been published concerning the functional significance of molecular variants. It has been shown that nucleotide variability within the long control region leads to differences in the binding affinity of some cellular transcriptional factors and to the enhancement of the expression of E6 and E7 oncogenes. Furthermore, in vivo and in vitro studies revealed differences in E6 and E7 biochemical and biological properties among molecular variants. Nevertheless, further correlation with additional functional information is needed to evaluate the significance of genome intratypic variability. These results are also important for the development of vaccines and to determine the extent to which immunization with L1 virus-like particles of one variant could induce antibodies that cross-neutralize other variants. Key words Papillomavirus heterogeneityThe first evidence for the existence of different human papillomavirus (HPV) types was obtained in the early 1970's when it was observed that mRNA purified from plantar warts hybridized with DNA purified from other plantar warts but not from warts at other sites, including anogenital ones. In the following years, the genetic heterogeneity of HPV was confirmed by restriction fragment length polymorphism analysis and this was followed by an extensive and clear definition of HPV types based on DNA sequencing of different genes and the long control region (LCR) (1).HPV types are defined as a viral genome with an L1 late gene sequence that is at least 10% dissimilar from that of any other type. To date more than 120 different HPV genotypes associated with infections in humans have been described. In addition, the Papillomavirus Nomenclature Committee has established that HPV genomes be classified into molecular variants when they present more than 98% of similarity to the prototype

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

“…Our preliminary findings showing high prevalence of HPV type 16 are concordant with other studies that show it to be the most common HPV and to be associated with over 50% of cases of cervical cancers (Muñoz, 2000;Sichero and Villa, 2006). This was also found in southeastern (Villa et al, 2000) and central Brazil (Cruz et al, 2004;Alencar et al, 2007).…”

Variant Lineages of Human Papillomavirus Type 18 in Northeast China Populations Characterized by Sequence Analysis of E6, E7, and L1 Regions

“…26,27 The previously described substitutions of R25Q, P91Q, P344R, and P399R of L1 were observed in all HPV 18 strains analyzed here, whereas the aa substitutions of A164V, Q334P/H, and D520N were novel mutations. These results extended the data about nucleotide and aa changes in the HPV-18 L1 region.…”

Impact of HPV infection on the development of head and neck cancer

“…Mostly, viral variants arise by nucleotide substitutions in few restricted positions within the entire genome. Nucleotide sequence analysis of HPV-16- and -18-positive cervical samples collected worldwide has categorized molecular variants into phylogenetically related lineages: European, Asian-American, Asian, and African 4. More recently, the nomenclature of variant lineages has been established for other HPV types 5,6.…”