Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection.
Chronic systemic immune activation significantly influences human immunodeficiency virus (HIV) disease progression. Despite evidence of a pro-inflammatory environment in the genital tract of HIV-infected women, comprehensive investigations into cervical tissue from this region remain limited. Simila...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-11-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012709 |
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| author | Mathias Franzén Boger Tyra Hasselrot Vilde Kaldhusdal Gisele H B Miranda Paulo Czarnewski Gabriella Edfeldt Frideborg Bradley Genta Rexaj Julie Lajoie Kenneth Omollo Joshua Kimani Keith R Fowke Kristina Broliden Annelie Tjernlund |
| author_facet | Mathias Franzén Boger Tyra Hasselrot Vilde Kaldhusdal Gisele H B Miranda Paulo Czarnewski Gabriella Edfeldt Frideborg Bradley Genta Rexaj Julie Lajoie Kenneth Omollo Joshua Kimani Keith R Fowke Kristina Broliden Annelie Tjernlund |
| author_sort | Mathias Franzén Boger |
| collection | DOAJ |
| description | Chronic systemic immune activation significantly influences human immunodeficiency virus (HIV) disease progression. Despite evidence of a pro-inflammatory environment in the genital tract of HIV-infected women, comprehensive investigations into cervical tissue from this region remain limited. Similarly, the consequences of chronic HIV infection on the integrity of the female genital epithelium are poorly understood, despite its importance in HIV transmission and replication. Ectocervical biopsies were obtained from HIV-seropositive (n = 14) and HIV-seronegative (n = 47) female Kenyan sex workers. RNA sequencing and bioimage analysis of epithelial junction proteins (E-cadherin, desmoglein-1, claudin-1, and zonula occludens-1) were conducted, along with CD4 staining. RNA sequencing revealed upregulation of immunoregulatory genes in HIV-seropositive women, primarily associated with heightened T cell activity and interferon signaling, which further correlated with plasma viral load. Transcription factor analysis confirmed the upregulation of pro-inflammatory transcription factors, such as RELA, NFKB1, and IKZF3, which facilitates HIV persistence in T cells. Conversely, genes and pathways associated with epithelial barrier function and structure were downregulated in the context of HIV. Digital bioimage analysis corroborated these findings, revealing significant disruption of various epithelial junction proteins in ectocervical tissues of the HIV-seropositive women. Thus, chronic HIV infection associated with ectocervical inflammation, characterized by induced T cell responses and interferon signaling, coupled with epithelial disruption. These alterations may influence HIV transmission and heighten susceptibility to other sexually transmitted infections. These findings prompt exploration of therapeutic interventions to address HIV-related complications and mitigate the risk of sexually transmitted infection transmission. |
| format | Article |
| id | doaj-art-3c9722b44e584aaba018940e8de71ebb |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-3c9722b44e584aaba018940e8de71ebb2024-12-10T05:31:18ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-11-012011e101270910.1371/journal.ppat.1012709Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection.Mathias Franzén BogerTyra HasselrotVilde KaldhusdalGisele H B MirandaPaulo CzarnewskiGabriella EdfeldtFrideborg BradleyGenta RexajJulie LajoieKenneth OmolloJoshua KimaniKeith R FowkeKristina BrolidenAnnelie TjernlundChronic systemic immune activation significantly influences human immunodeficiency virus (HIV) disease progression. Despite evidence of a pro-inflammatory environment in the genital tract of HIV-infected women, comprehensive investigations into cervical tissue from this region remain limited. Similarly, the consequences of chronic HIV infection on the integrity of the female genital epithelium are poorly understood, despite its importance in HIV transmission and replication. Ectocervical biopsies were obtained from HIV-seropositive (n = 14) and HIV-seronegative (n = 47) female Kenyan sex workers. RNA sequencing and bioimage analysis of epithelial junction proteins (E-cadherin, desmoglein-1, claudin-1, and zonula occludens-1) were conducted, along with CD4 staining. RNA sequencing revealed upregulation of immunoregulatory genes in HIV-seropositive women, primarily associated with heightened T cell activity and interferon signaling, which further correlated with plasma viral load. Transcription factor analysis confirmed the upregulation of pro-inflammatory transcription factors, such as RELA, NFKB1, and IKZF3, which facilitates HIV persistence in T cells. Conversely, genes and pathways associated with epithelial barrier function and structure were downregulated in the context of HIV. Digital bioimage analysis corroborated these findings, revealing significant disruption of various epithelial junction proteins in ectocervical tissues of the HIV-seropositive women. Thus, chronic HIV infection associated with ectocervical inflammation, characterized by induced T cell responses and interferon signaling, coupled with epithelial disruption. These alterations may influence HIV transmission and heighten susceptibility to other sexually transmitted infections. These findings prompt exploration of therapeutic interventions to address HIV-related complications and mitigate the risk of sexually transmitted infection transmission.https://doi.org/10.1371/journal.ppat.1012709 |
| spellingShingle | Mathias Franzén Boger Tyra Hasselrot Vilde Kaldhusdal Gisele H B Miranda Paulo Czarnewski Gabriella Edfeldt Frideborg Bradley Genta Rexaj Julie Lajoie Kenneth Omollo Joshua Kimani Keith R Fowke Kristina Broliden Annelie Tjernlund Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection. PLoS Pathogens |
| title | Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection. |
| title_full | Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection. |
| title_fullStr | Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection. |
| title_full_unstemmed | Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection. |
| title_short | Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection. |
| title_sort | sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic hiv infection |
| url | https://doi.org/10.1371/journal.ppat.1012709 |
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