Dataset Information

Paracrine Signals from HIV-1 Infected Immune Cells Reprogram Cervical Cancer Pathways

ABSTRACT: Co-infection of human papillomavirus (HPV) and human immunodeficiency virus type 1 (HIV-1) in women have a six-fold higher risk of developing cervical cancer compared to those without HIV. To evaluate how paracrine signals from HIV-infected T-cells remodeled the proteome of cervical epithelial cells in culture, primary CD4+ T cells isolated from PBMC-enriched leukapheresis products (leukopaks) from two healthy donors were infected or uninfected with a replication-competent pNL4-3 HIV-1 strain for 72 hours. Secretome from the CD4+ T cell cultures was used to stimulate the human HPV-negative cervical epithelial cell line, C33A, for 72 hours. Then, C33A cells were harvested, and cell lysates were digested and subjected to global quantitative mass spectrometry (MS) based abundance proteomics and phosphoproteomics analyses. Both proteomics and phosphoproteomics outputs were analysed using bioinformatics approaches. These datasets revealed altered expression of proteins in the MAPK, PI3K-AKT, and β-catenin signaling pathways. Additionally, MS phosphoproteomics analysis confirmed PI3K-AKT pathway activation in cervical cells exposed to conditioned media from HIV-1-infected T cells.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Cell Culture, Epithelial Cell Of Cervix

DISEASE(S): Human Immunodeficiency Virus Infectious Disease

SUBMITTER: Mehdi Bouhaddou

LAB HEAD: Mehdi Bouhaddou

PROVIDER: PXD064529 | Pride | 2026-06-25

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20240416_120206_2024-04-16_CharlesOlwal_HIV.sne	Other
	20241011_122123_C33A_UCSF_PP.sne	Other
	HIV_vector_pNL4_3.fasta	Fasta
	Raw_files_abundance.zip	Other
	Raw_files_phospho.zip	Other

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Publications

Paracrine signals from HIV-1-infected immune cells reprogram cervical cancer pathways.

Olwal Charles Ochieng' CO Rathore Ujjwal U Makanani Sara K SK Kaushal Prashant P Ashley Immy A IA Ummadi Manisha R MR Appiah Vincent V Djomkam Zune Alexandra Lindsey AL Blanc Sophie F SF Winters Declan M DM Delgado Yennifer Y Muthoka Kapten K Fabius Jacqueline M JM Eckhardt Manon M Kaake Robyn M RM Su Maureen M Fregoso Oliver I OI Hultquist Judd F JF Orang'o Elkanah Omenge EO Swaney Danielle L DL Kyei George Boateng GB Krogan Nevan J NJ Quashie Peter Kojo PK Bediako Yaw Y Bouhaddou Mehdi M

iScience 20260604 6

Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary cause of cervical cancer. Co-infection with HIV-1 increases the risk of cervical cancer progression 6-fold, despite adherence to antiretroviral therapy (ART). While chronic HIV-1 infection is known to cause inflammation, the paracrine effects of HIV-1-infected immune cells on cervical signaling remain unclear. We performed transcriptomics on cervical swabs from Kenyan women stratified by HIV-1 and cancer status, whi ...[more]

PMID: 42305618

Similar Datasets

Project description:HIV-1 infections of women are mainly acquired through female reproductive tract where cervical and vaginal epithelial cells are the first line of defense. Although HIV-1 does not directly infect epithelial cells, HIV-1 obligatorily interacts with and crosses over epithelial layer to infect susceptible target cells, mainly CD4+ T cells, in the lamina propria to initiate an infection. However, the mechanism and ramification of the interaction of HIV-1 and epithelial cells in vaginal transmission of HIV-1 remain to be elucidated. We hypothesized that cervical epithelial cells are not a passive barrier, but actively respond to HIV-1 to change mucosal milieu and facilitate HIV-1 transmission. We tested this hypothesis by studying the responses of cervical epithelial cells to HIV-1 through profiling genome-wide transcription. We found 1) cervical epithelial cells actively respond to HIV-1. Five hundred forty-three transcripts/genes in cervical epithelial cells were significantly altered in expression at four hours post exposure to HIV-1, of which many relate to important signaling pathways, such as innate immune responses, pattern recognition receptors, apoptosis, biosynthesis, and energy production, 2) HIV-1 increases the expression of CXC Chemokines (IL-8, CXCL1 and CXCL3) in cervical epithelial cells. IL-8 and CXCL1 are potent chemotactic for multinuclear neutrophils (MNP), monocytes and a minority of lymphocytes, and CXCL3 is predominant chemotactic for monocytes, 3) HIV-1 increases the expression of key inflammatory enzymes-COX-1 and COX-2. COX-1 is responsible for the production of prostaglandins that are important for homeostatic functions, and COX-2 is a key enzyme to convert arachidonic acid to prostaglandins, key inflammatory mediators, and 4) the increased expression of IL-8 and COX-2 revealed using microarray analysis was mapped into the endocervical epithelial cells of macaques inoculated with inactivated SIV in vivo. Our date lead to a role model of epithelial cells in HIV-1 vaginal transmission, that is the axis of HIV-1, epithelial cells, proinflammatory molecules (IL-8, CXCL1, CXCL3, COX-1 and COX-2), cell recruitment (MNP, monocytes and T cells), and inflammation. This model implies that moderating epithelial proinflammatory response to HIV-1 may be utilized in prevention of HIV vaginal transmission.