Open this publication in new window or tab >>Science for Life Laboratory, Department of Biochemistry and Biophysics and National Bioinformatics Infrastructure Sweden, Stockholm University, Stockholm, Sweden,.
Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden,.
Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden,.
Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden,.
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada,.
Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya,.
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada,; Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya,; Partners for Health and Development in Africa, Nairobi, Kenya,.
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada,; Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya,; Partners for Health and Development in Africa, Nairobi, Kenya,; Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada.
Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden,.
Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden,.
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2024 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 20, no 11, article id e1012709Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2024
National Category
Infectious Medicine Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:kth:diva-357163 (URN)10.1371/journal.ppat.1012709 (DOI)001359211200004 ()39561211 (PubMedID)2-s2.0-85209895760 (Scopus ID)
Note
QC 20241205
2024-12-042024-12-042025-02-20Bibliographically approved