Cervicovaginal Human Papillomavirus Genomes, Microbiota Composition and Cytokine Concentrations in South African Adolescents

Abstract

The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15–19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with a focus on human papillomavirus (HPV) genomes and relate these to the vaginal bacterial microbiota (assessed by 16S rRNA gene sequencing) and cytokines (assessed by Luminex). The DNA virome included single-stranded (Anelloviridae, Genomoviridae) and double-stranded DNA viruses (Adenoviridae, Alloherpesviridae, Herpesviridae, Marseilleviridae, Mimiviridae, Polyomaviridae, Poxviridae). We identified 110 unique, complete HPV genomes within two genera (Alphapapillomavirus and Gammapapillomavirus) representing 40 HPV types and 12 species. Of the 40 HPV types identified, 35 showed positive co-infection patterns with at least one other type, mainly HPV-16. HPV-35, a high-risk genotype currently not targeted by available vaccines, was the most prevalent HPV type identified in this cohort. Bacterial taxa commonly associated with bacterial vaginosis also correlated with the presence of HPV. Bacterial vaginosis, rather than HPV, was associated with increased genital inflammation. This study lays the foundation for future work characterizing the vaginal virome and its role in women’s health.

Characterization of CRESS‐DNA viruses in human vaginal secretions: An exploratory metagenomic investigation

“…There has been a paucity of whole‐genome sequences for eukaryote‐infecting CRESS‐DNA viruses isolated from the female genital tract. Currently, both the Metagenomic tools and the rolling‐circle replication methods for sequence amplification have favored the identification and annotation of a repertory of novel CRESS‐DNA viruses and the discovery of their range of eukaryotic hosts 6,7,32 . Our findings underscore the substantial diversity within CRESS‐DNA viruses.…”

“…Detection of eukaryote‐infecting CRESS‐DNA viruses in cervical samples from young African adolescent women were reported in the presence of Anelloviridae and Genomoviridae , although most studies of the vaginal virome were limited to report of double‐stranded DNA viruses, with an emphasis on HPV genomes 32,33 . In addition, the simultaneous presence of fungi DNA and Genomovirus was found in a subset of cervical swabs from HIV/HPV co‐infected women in which both virome and bacteriome composition were analyzed 34 .…”

“…This virus family also has the potential to infect fungi present in the cervico‐vaginal region of HIV‐positive women carrying both Candida albicans and Genomovirus 34 . Conversely, two studies reported Genomovirus in cervico‐vaginal samples from healthy South African adolescent women 32,33 . In addition, the oral amoeba Entamoeba gingivalis has been identified as a likely host of redondoviruses 36 …”

High-risk human papillomavirus prevalence among South African women diagnosed with other STIs and BV

“…STIs such as Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis have been associated with HPV infection and persistence, leading to delayed infection clearance and possible induction of precancerous lesions or cervical intraepithelial neoplasia (CIN) type 1, 2, or 3 [15,16]. Furthermore, bacterial vaginosis (BV), the most common cause of abnormal vaginal discharge among women of childbearing age, is associated with incident HPV infection and HPV persistence [17,18]. The high prevalence of BV and multiple infections with sexually transmitted pathogens (such as HPV and other STIs) has been associated with increased HIV acquisition risk in sub-Saharan African women [19][20][21].…”