INTRATYPE VARIATION IN 12 HUMAN PAPILLOMAVIRUS TYPES - A WORLDWIDE PERSPECTIVE

In this study, we have examined intratype human papillomavirus (HPV) s equence variation in a worldwide collection of cervical specimens. Twe lve different HPV types including HPV-18, HPV-33, HPV-35, HPV-39, HPV- 45, HPV-51, HPV-52, HPV-58, HPV-59, HPV-68 (ME180), MM9/PAP238A (recen tly designated HPV-73), and a novel partial genomic HPV sequence desig nated MM4/W13B were analyzed in this study. Cervical specimens were co llected as part of epidemiological investigations conducted in New Mex ico and an international study of invasive cervical cancer (IBSCC). Sp ecimens from several countries including Argentina, Brazil, Bolivia, B enin, Cuba, Colombia, Chile, Germany, Mall, Panama, Paraguay, Spain, A lgeria, Uganda, Guinea, Tanzania, Indonesia, Philippines, Thailand, an d the United States were evaluated. Specimen DNAs were subjected to am plification with the MY09/11 L1 consensus PCR system. The PCR products were cloned, and an approximately 410-bp region in the L1 open readin g frame was sequenced from 146 specimens (similar to 60,000 bp). Withi n a single HPV type, nucleotide diversity varied between 0.2 and 2.9% (i.e., between any pair of variants) and the majority of nucleotide ch anges were synonymous (amino acid conserving). These data provide;info rmation pertinent to HPV diagnostic probe development and are potentia lly relevant to future rational vaccine strategies. Similarly, amino a cid diversity varied between 0 and 5.1%. Some of these amino acid chan ges may represent markers of intertype evolutionary relationships. Pre suming that HPVs have evolved under the same constraints as their corr esponding hosts, the limited genetic diversity observed for all HPVs s tudied to date may reflect an evolutionary bottleneck occurring in bot h virus and host populations.