Cervicovaginal DNA Virome Alterations Are Associated with Genital Inflammation and Microbiota Composition

Kaelin, Emily A; Skidmore, Peter T; Łaniewski, Paweł; Holland, LaRinda A; Chase, Dana M.; Herbst-Kralovetz, Melissa M.; Lim, Efrem S.

doi:10.1128/msystems.00064-22

Cited by 19 publications

(16 citation statements)

References 55 publications

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“…The association between TTV and higher levels of Sneathia and Shuttleworthia probably goes in the same direction. In fact, genital inflammation can be linked to specific BV-related microorganisms, including Sneathia (Kaelin et al, 2022). As reported by Lopez-Filloy et al, women with HPV infection are characterized by a significant increase in anaerobes, such as Sneathia and Shuttleworthia, their presence being in turn associated to a higher level of cervico-vaginal inflammation and a higher risk of BV recurrence (López-Filloy et al, 2022).…”

Section: Discussionmentioning

confidence: 93%

Torquetenovirus in pregnancy: Correlation with vaginal microbiome, metabolome and pro-inflammatory cytokines

et al. 2022

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Torquetenovirus (TTV) is a negative sense, single-stranded DNA virus present in many body fluids of apparently healthy individuals. At present, it is considered a non-pathogenic endogenous virus. TTV can be detected in the vagina of pregnant women, its abundance being modulated with the extent of immune system activation. Until now, there is only scarce information regarding the association between TTV and the composition of the vaginal environment. Therefore, this study aimed to assess the presence of TTV in the vaginal ecosystem of a cohort of white women with a normal pregnancy (n = 60) at different gestational stages (first, second and third trimester) and in 9 subjects suffering a first trimester miscarriage. For each woman, we determined (i) the presence and titer of TTV, (ii) the vaginal bacterial composition by means of Nugent score and 16S rRNA gene sequencing, (iii) the vaginal metabolic profiles through 1H-NMR spectroscopy, and (iv) the vaginal concentration of two pro-inflammatory cytokines (IL-6 and IL-8). More than one third of women were found negative for TTV at all gestational stages. Although not statistically significant, the positivity for TTV dropped from 53.3% in the first to 36.6% in the third trimester. TTV loads varied greatly among vaginal samples, ranging between 2 × 101 and 2 × 105 copies/reaction. No difference in TTV prevalence and loads was observed between women with normal pregnancies and miscarriages. The presence of TTV was more common in women with a higher vaginal leucocyte count (p = 0.02). The levels of IL-6 (p = 0.02), IL-8 (p = 0.03), propionate (p = 0.001) and cadaverine (p = 0.006) were significantly higher in TTV-positive samples. TTV titer was positively correlated with the concentrations of 4-hydroxyphenyllactate (p < 0.0001), isoleucine (p = 0.01) and phenylalanine (p = 0.04). TTV-positive samples were characterized by a higher relative abundance of Sneathia (p = 0.04) and Shuttleworthia (p = 0.0009). In addition, a trend toward a decrease of Lactobacillus crispatus and Lactobacillus jensenii, and an increase of Lactobacillus iners was observed for TTV-positive samples. In conclusion, we found that TTV is quite common in women with normal pregnancy outcomes, representing a possible predictor of local immune status.

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Section: Discussionmentioning

confidence: 93%

Torquetenovirus in pregnancy: Correlation with vaginal microbiome, metabolome and pro-inflammatory cytokines

et al. 2022

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“…There was a higher prevalence of AVs in HPV+ women and literature associate these coinfections not only in cervix, but also at other sites ( 53 – 55 ). It has been suggested that coinfection contributes to laryngeal carcinoma progression ( 55 , 56 ) and magnifies immune responses ( 57 – 59 ), creating a microenvironment that favours their establishment and facilitates tumor development.…”

Section: Discussionmentioning

confidence: 99%

Microbiome analysis of Brazilian women cervix reveals specific bacterial abundance correlation to RIG-like receptor gene expression

et al. 2023

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The relationship among microbiome, immunity and cervical cancer has been targeted by several studies, yet many questions remain unanswered. We characterized herein the virome and bacteriome from cervical samples and correlated these findings with innate immunity gene expression in a Brazilian convenience sample of HPV-infected (HPV+) and uninfected (HPV-) women. For this purpose, innate immune gene expression data were correlated to metagenomic information. Correlation analysis showed that interferon (IFN) is able to differentially modulate pattern recognition receptors (PRRs) expression based on HPV status. Virome analysis indicated that HPV infection correlates to the presence of Anellovirus (AV) and seven complete HPV genomes were assembled. Bacteriome results unveiled that vaginal community state types (CST) distribution was independent of HPV or AV status, although bacterial phyla distribution differed between groups. Furthermore, TLR3 and IFNαR2 levels were higher in the Lactobacillus no iners-dominated mucosa and we detected correlations among RIG-like receptors (RLR) associated genes and abundance of specific anaerobic bacteria. Collectively, our data show an intriguing connection between HPV and AV infections that could foster cervical cancer development. Besides that, TLR3 and IFNαR2 seem to create a protective milieu in healthy cervical mucosa (L. no iners-dominated), and RLRs, known to recognize viral RNA, were correlated to anaerobic bacteria suggesting that they might be related to dysbiosis.

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“…Infection with HPV may play all these roles. On the other hand, genital inflammation was previously reported to be associated with a decreasing diversity of cervicovaginal DNA viruses [ 57 ]. However, genital inflammation samples were excluded from our study.…”

Section: Discussionmentioning

confidence: 99%

Cervical Microbiome in Women Infected with HPV16 and High-Risk HPVs

Sasivimolrattana

Chantratita

Sensorn

et al. 2022

IJERPH

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Human papillomavirus type 16 (HPV16) and/or high-risk (Hr-) HPV are the main causes of cervical cancer. Another element that may contribute to the development of cervical cancer is the microbiota. To date, no study has investigated the entire cervical microbiome, which consists of bacteria, fungi, and viruses. In this study, cervical samples with different histopathology (CIN1, CIN2, and CIN3), with or without HPV16 and Hr-HPVs infection, were enrolled. From bacterial community analysis, 115 bacterial species were found and separated into 2 distinct categories based on Lactobacillus abundance: Lactobacilli-dominated (LD) and non-Lactobacilli-dominated (NLD) groups. The LD group had significantly less bacterial diversity than the NLD group. In addition, the variety of bacteria was contingent on the prevalence of HPV infection. Among distinct histological groups, an abundance of L. iners (>60% of total Lactobacillus spp.) was discovered in both groups. A few fungi, e.g., C. albicans, were identified in the fungal community. The viral community analysis revealed that the presence of HPV considerably reduced the diversity of human viruses. Taken together, when we analyzed all our results collectively, we discovered that HPV infection was a significant determinant in the diversity of bacteria and human viruses in the cervix.

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Cervicovaginal DNA Virome Alterations Are Associated with Genital Inflammation and Microbiota Composition

Abstract: HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood.

Cited by 19 publications

References 55 publications

Torquetenovirus in pregnancy: Correlation with vaginal microbiome, metabolome and pro-inflammatory cytokines

Torquetenovirus in pregnancy: Correlation with vaginal microbiome, metabolome and pro-inflammatory cytokines

Microbiome analysis of Brazilian women cervix reveals specific bacterial abundance correlation to RIG-like receptor gene expression

Cervical Microbiome in Women Infected with HPV16 and High-Risk HPVs

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