TY - JOUR
T1 - Cervicovaginal DNA Virome Alterations Are Associated with Genital Inflammation and Microbiota Composition
AU - Kaelin, Emily A.
AU - Skidmore, Peter T.
AU - Łaniewski, Paweł
AU - Holland, La Rinda A.
AU - Chase, Dana M.
AU - Herbst-Kralovetz, Melissa M.
AU - Lim, Efrem S.
N1 - Funding Information:
We thank the study participants. This research was funded by Arizona State University (E.S.L.), NIH grants R00DK107923 (E.S.L.) and R01HD092311 (E.S.L.), and Flinn Foundation grant 2244 (D.M.C. and M.M.H.-K.). Conceptualization: M.M.H.-K., E.S.L.; Data curation: E.A.K., P.T.S., P.Ł.; Formal analysis: E.A.K., P.T.S.; Funding acquisition: D.M.C., M.M.H.-K., E.S.L.; Investigation: E.A.K., P.T.S., L.A.H., E.S.L.; Resources: P.Ł., D.M.C., M.M.H.-K.; Supervision: E.S.L.; Visualization: E.A.K., P.T.S.; Writing – original draft: E.A.K., P.T.S., E.S.L.; Writing – review & editing: E.A.K., P.Ł., M.M.H.-K., E.S.L. All authors reviewed and approved the final manuscript. We declare no competing interests.
Publisher Copyright:
Copyright © 2022 Kaelin et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2022/4
Y1 - 2022/4
N2 - While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. £aniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/ 10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4: 58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171-180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123-137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7: 10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic nextgeneration sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus. Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women's health.
AB - While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. £aniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/ 10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4: 58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171-180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123-137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7: 10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic nextgeneration sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus. Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women's health.
KW - HPV
KW - Lactobacillus species
KW - anellovirus
KW - cervical cancer
KW - cervicovaginal virome
KW - genital inflammation
KW - human papillomavirus
KW - transkingdom interactions
KW - vaginal microbiome
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U2 - 10.1128/msystems.00064-22
DO - 10.1128/msystems.00064-22
M3 - Article
AN - SCOPUS:85129092100
SN - 2379-5077
VL - 7
JO - mSystems
JF - mSystems
IS - 2
ER -