Abstract
ObjectivesTo determine the prevalence, viral load, tissue tropism, and genetic variability of novel human papillomavirus (HPV) type 179, which is etiologically associated with sporadic cases of common warts in immunocompromised patients, and phylogenetically related HPV types 135 and 146.MethodsThe representative collection of 850 HPV-associated clinical samples (oral/nasopharyngeal/anal, archival specimens of oral/oropharyngeal/conjunctival/cervical/skin cancer, benign lesions of the larynx/conjunctiva/skin, and eyebrows), obtained from immunocompetent individuals, was tested for the presence of HPV179, HPV135, and HPV146 using type-specific real-time PCRs. To assess the genetic diversity of the HPVs investigated in the non-coding long control region (LCR), several highly sensitive nested PCR protocols were developed for each HPV type. The genetic diversity of HPV179 was additionally determined in 12 HPV179 isolates from different anatomical sites of an only immunocompromised patient included in the study.ResultsHPV179, HPV135, and HPV146 were detected in 1.4, 2.0, and 1.5% of the samples tested, respectively, with no preference for cutaneous or mucosal epithelial cells. One (with five single nucleotide polymorphisms; SNPs), four (with one to six SNPs), and four (with one to eight SNPs) genetic variants of HPV179, HPV135, and HPV146, respectively, were identified among eligible samples. HPV179 isolates from the immunocompromised patient exhibited the identical LCR nucleotide sequence, suggesting that HPV179 can cause generalized HPV infections.ConclusionsHPV179, HPV135, and HPV146 have a mucocutaneous tissue tropism and are associated with sporadic infections in immunocompromised and immunocompetent individuals. Because the majority of mutations were found outside the major functional domains of the respective LCRs, we assume that HPV179, HPV135, and HPV146 genetic variants pathogenically do not differ from their prototypes. In addition, no association was found between specific HPV179, HPV135, and HPV146 genetic variants and anatomical sites of infection and/or specific neoplasms.
Highlights
Human papillomaviruses (HPVs) are small, non-enveloped DNA viruses that cluster into five different papillomavirus (PV) genera—Alphapapillomavirus (Alpha-PV), Betapapillomavirus (Beta-PV), Gammapapillomavirus (Gamma-PV), Mupapillomavirus (Mu-PV), and Nupapillomavirus (Nu-PV)—based on the nucleotide similarities of their L1 genes [1]
HPV179 isolates from the immunocompromised patient exhibited the identical long control region (LCR) nucleotide sequence, suggesting that HPV179 can cause generalized HPV infections
Because the majority of mutations were found outside the major functional domains of the respective LCRs, we assume that HPV179, HPV135, and HPV146 genetic variants pathogenically do not differ from their prototypes
Summary
Human papillomaviruses (HPVs) are small, non-enveloped DNA viruses that cluster into five different papillomavirus (PV) genera—Alphapapillomavirus (Alpha-PV), Betapapillomavirus (Beta-PV), Gammapapillomavirus (Gamma-PV), Mupapillomavirus (Mu-PV), and Nupapillomavirus (Nu-PV)—based on the nucleotide similarities of their L1 genes [1]. Gamma-PVs have frequently been detected in histologically normal skin [4,5,6,7,8,9,10] in several mucosal anatomical sites, including oral, nasal, and cervical mucosa [11,12,13,14], and in the mucocutaneous epithelium of the penis and anal canal [15,16] Their presence has been demonstrated in Alpha-PV-negative anogenital warts [17,18] and cervical intraepithelial lesions [11,19,20,21,22]. Some previous studies proposed a potential active role of Gamma-PVs in the development of skin warts [23], premalignant cutaneous lesions [24,25] and head and neck cancer [26]
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