Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment.
To better understand the molecular mechanism that drives neuroinflammation, we analyzed the protein profiles of 27 brains from HIV with HIV (PWH) on antiretroviral therapy (ART), including various stages of HIV-associated neurocognitive disorders (HAND), and compared them to 9 HAND-negative controls...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-08-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013411 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849228207411167232 |
|---|---|
| author | Yuyang Tang Ling Xie Ciniso Sylvester Shabangu Dajiang Li Gabriela da Silva Prates Ashokkumar Manickam Lilly M Wong Antoine Chaillon Edward P Browne Sara Gianella Wenzhe Ho David M Margolis Xian Chen Wenhui Hu Guochun Jiang |
| author_facet | Yuyang Tang Ling Xie Ciniso Sylvester Shabangu Dajiang Li Gabriela da Silva Prates Ashokkumar Manickam Lilly M Wong Antoine Chaillon Edward P Browne Sara Gianella Wenzhe Ho David M Margolis Xian Chen Wenhui Hu Guochun Jiang |
| author_sort | Yuyang Tang |
| collection | DOAJ |
| description | To better understand the molecular mechanism that drives neuroinflammation, we analyzed the protein profiles of 27 brains from HIV with HIV (PWH) on antiretroviral therapy (ART), including various stages of HIV-associated neurocognitive disorders (HAND), and compared them to 9 HAND-negative controls. We found that most of the proteins that were increased-about 66.7%-were involved in immune response pathways. Of these, 23.3% were specifically related to type I interferon (IFN-I) signaling, which remains active in the brain through both HIV-related and unrelated mechanisms. Using single-cell RNA sequencing (scRNA-seq) on brain tissues collected during rapid autopsies from participants in the Last Gift cohort, we found that IFN-I signaling was especially strong in astrocytes, microglia (MG), and endothelial cells. In a mini-brain organoid model of acute HIV infection, IFN-I signaling was also highly active in astrocytes but less so in MG. Interestingly, IFN-I activation can happen without HIV being present-expression of human endogenous retrovirus-W1 (HERV-W1) Env can directly trigger this response in astrocytes, and it continues in glial cells even with effective ART. Together, our findings point to persistent IFN-I activation in glial and endothelial cells in the brain, which may contribute to neuroinflammation and cognitive disorders in PWH on ART. |
| format | Article |
| id | doaj-art-29537e3cebf94eeb9556f6e1f5d66221 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-29537e3cebf94eeb9556f6e1f5d662212025-08-23T05:31:26ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-08-01218e101341110.1371/journal.ppat.1013411Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment. Yuyang TangLing XieCiniso Sylvester ShabanguDajiang LiGabriela da Silva PratesAshokkumar ManickamLilly M WongAntoine ChaillonEdward P BrowneSara GianellaWenzhe HoDavid M MargolisXian ChenWenhui HuGuochun JiangTo better understand the molecular mechanism that drives neuroinflammation, we analyzed the protein profiles of 27 brains from HIV with HIV (PWH) on antiretroviral therapy (ART), including various stages of HIV-associated neurocognitive disorders (HAND), and compared them to 9 HAND-negative controls. We found that most of the proteins that were increased-about 66.7%-were involved in immune response pathways. Of these, 23.3% were specifically related to type I interferon (IFN-I) signaling, which remains active in the brain through both HIV-related and unrelated mechanisms. Using single-cell RNA sequencing (scRNA-seq) on brain tissues collected during rapid autopsies from participants in the Last Gift cohort, we found that IFN-I signaling was especially strong in astrocytes, microglia (MG), and endothelial cells. In a mini-brain organoid model of acute HIV infection, IFN-I signaling was also highly active in astrocytes but less so in MG. Interestingly, IFN-I activation can happen without HIV being present-expression of human endogenous retrovirus-W1 (HERV-W1) Env can directly trigger this response in astrocytes, and it continues in glial cells even with effective ART. Together, our findings point to persistent IFN-I activation in glial and endothelial cells in the brain, which may contribute to neuroinflammation and cognitive disorders in PWH on ART.https://doi.org/10.1371/journal.ppat.1013411 |
| spellingShingle | Yuyang Tang Ling Xie Ciniso Sylvester Shabangu Dajiang Li Gabriela da Silva Prates Ashokkumar Manickam Lilly M Wong Antoine Chaillon Edward P Browne Sara Gianella Wenzhe Ho David M Margolis Xian Chen Wenhui Hu Guochun Jiang Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment. PLoS Pathogens |
| title | Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment. |
| title_full | Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment. |
| title_fullStr | Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment. |
| title_full_unstemmed | Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment. |
| title_short | Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment. |
| title_sort | persistent type i interferon signaling within the brain of people with hiv on art with cognitive impairment |
| url | https://doi.org/10.1371/journal.ppat.1013411 |
| work_keys_str_mv | AT yuyangtang persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT lingxie persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT cinisosylvestershabangu persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT dajiangli persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT gabrieladasilvaprates persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT ashokkumarmanickam persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT lillymwong persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT antoinechaillon persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT edwardpbrowne persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT saragianella persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT wenzheho persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT davidmmargolis persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT xianchen persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT wenhuihu persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment AT guochunjiang persistenttypeiinterferonsignalingwithinthebrainofpeoplewithhivonartwithcognitiveimpairment |