Genomic diversity and interspecies host infection of alpha12 Macaca fascicularis papillomaviruses (MfPVs).

Alpha human papillomaviruses (HPVs) are among the most common sexually transmitted agents of which a subset causes cervical neoplasia and cancer in humans. Alpha-PVs have also been identified in non-human primates although few studies have systematically characterized such types. We cloned and characterized 10 distinct types of PVs from exfoliated cervicovaginal cells from different populations of female cynomolgus macaques (Macaca fascicularis) originating from China and Indonesia. These include 5 novel genotypes and 5 previously identified genotypes found in rhesus (Macaca mulatta) (RhPV-1, RhPV-a, RhPV-b and RhPV-d) and cynomolgus macaques (MfPV-a). Type-specific primers were designed to amplify the complete PV genomes using an overlapping PCR method. Four MfPVs were associated with cervical intraepithelial neoplasia (CIN). The most prevalent virus type was MfPV-3 (formerly RhPV-d), which was identified in 60% of animals with CIN. In addition, the complete genomes of variants of MfPV-3 and RhPV-1 were characterized. These variants are 97.1% and 97.7% similar across the L1 nucleotide sequences with the prototype genomes, respectively. Sequence comparisons and phylogenetic analyses indicate that these novel MfPVs cluster together within the alpha12 PV species closely related to the alpha9 (e.g., HPV16) and alpha11 species (e.g., HPV34), and all share a most recent common ancestor. Our data expand the molecular diversity of non-human primate PVs and suggest a recent expansion of alpha-PV species groups. Moreover, identification of an overlapping set of MfPVs in rhesus and cynomolgus macaques indicates that non-human primate alpha-PVs might not be strictly species-specific and may represent past interspecies infection.