Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx
(2025) In International Journal of Molecular Sciences 26(8).- Abstract
Viral protein X (Vpx) is a unique accessory protein encoded by the genome of the human immunodeficiency virus type 2 (HIV-2) and lineages of the simian immunodeficiency virus of sooty mangabeys. So far, counteracting the cellular restriction factor SAMHD1 and mediating the efficient translocation of viral pre-integration complex have been recognized as key functions of Vpx; however, a thorough exploration of its effects on the cellular transcriptome and cytokine milieu has not yet been undertaken. In this study, we carried out the transcriptomic analysis of THP-1 cells and determined differential gene expressions induced by HIV-2 Vpx, utilizing vectors coding for the wild-type and K68-R70 functionally restricted proteins. Significantly... (More)
Viral protein X (Vpx) is a unique accessory protein encoded by the genome of the human immunodeficiency virus type 2 (HIV-2) and lineages of the simian immunodeficiency virus of sooty mangabeys. So far, counteracting the cellular restriction factor SAMHD1 and mediating the efficient translocation of viral pre-integration complex have been recognized as key functions of Vpx; however, a thorough exploration of its effects on the cellular transcriptome and cytokine milieu has not yet been undertaken. In this study, we carried out the transcriptomic analysis of THP-1 cells and determined differential gene expressions induced by HIV-2 Vpx, utilizing vectors coding for the wild-type and K68-R70 functionally restricted proteins. Significantly altered genes were then validated and quantified through real-time quantitative PCR (qPCR); additionally, replication-competent virions were also used to confirm the findings. Moreover, we analyzed the effect of Vpx expression on the secretion of key cytokines in the medium of transfected cells. Our findings revealed that wild-type HIV-2 Vpx can significantly alter the expression of genes coding for helicases, zinc finger proteins, chaperons, transcription factors and proteins involved in DNA methylation. Differentially altered genes were involved in negative regulation of viral processes, the type I interferon-signaling pathway, DNA-template transcription, elongation, the positive regulation of interferon beta production and the negative regulation of innate immune response. Importantly, Vpx was also found to decrease the expression of HIV-1 Tat, possibly through the downregulation of a crucial splicing factor, required for the maturation of Tat. Additionally, studies on cellular cytokine milieu showed that this accessory protein induced key proinflammatory cytokines. Our study provides important information about the complex role played by HIV-2 Vpx in priming and taming the cellular environment to allow for the establishment of the infection.
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- author
- Szojka, Zsófia Ilona LU ; Kunkli, Balázs ; Kiarie, Irene Wanjiru ; Linkner, Tamás Richárd ; Al-Muffti, Aya Shamal ; Ahmad, Hala ; Benkő, Szilvia ; Jansson, Marianne LU ; Tőzsér, József and Mahdi, Mohamed
- organization
- publishing date
- 2025-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cytokines, HIV-2, host response, transcriptional regulation, viral pathogenesis, Vpx
- in
- International Journal of Molecular Sciences
- volume
- 26
- issue
- 8
- article number
- 3460
- publisher
- MDPI AG
- external identifiers
-
- pmid:40331967
- scopus:105003781418
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms26083460
- language
- English
- LU publication?
- yes
- id
- ce7345a4-f931-4632-8ae0-d24738260c0a
- date added to LUP
- 2025-08-15 11:35:31
- date last changed
- 2025-08-16 03:00:06
@article{ce7345a4-f931-4632-8ae0-d24738260c0a,
abstract = {{<p>Viral protein X (Vpx) is a unique accessory protein encoded by the genome of the human immunodeficiency virus type 2 (HIV-2) and lineages of the simian immunodeficiency virus of sooty mangabeys. So far, counteracting the cellular restriction factor SAMHD1 and mediating the efficient translocation of viral pre-integration complex have been recognized as key functions of Vpx; however, a thorough exploration of its effects on the cellular transcriptome and cytokine milieu has not yet been undertaken. In this study, we carried out the transcriptomic analysis of THP-1 cells and determined differential gene expressions induced by HIV-2 Vpx, utilizing vectors coding for the wild-type and K68-R70 functionally restricted proteins. Significantly altered genes were then validated and quantified through real-time quantitative PCR (qPCR); additionally, replication-competent virions were also used to confirm the findings. Moreover, we analyzed the effect of Vpx expression on the secretion of key cytokines in the medium of transfected cells. Our findings revealed that wild-type HIV-2 Vpx can significantly alter the expression of genes coding for helicases, zinc finger proteins, chaperons, transcription factors and proteins involved in DNA methylation. Differentially altered genes were involved in negative regulation of viral processes, the type I interferon-signaling pathway, DNA-template transcription, elongation, the positive regulation of interferon beta production and the negative regulation of innate immune response. Importantly, Vpx was also found to decrease the expression of HIV-1 Tat, possibly through the downregulation of a crucial splicing factor, required for the maturation of Tat. Additionally, studies on cellular cytokine milieu showed that this accessory protein induced key proinflammatory cytokines. Our study provides important information about the complex role played by HIV-2 Vpx in priming and taming the cellular environment to allow for the establishment of the infection.</p>}},
author = {{Szojka, Zsófia Ilona and Kunkli, Balázs and Kiarie, Irene Wanjiru and Linkner, Tamás Richárd and Al-Muffti, Aya Shamal and Ahmad, Hala and Benkő, Szilvia and Jansson, Marianne and Tőzsér, József and Mahdi, Mohamed}},
issn = {{1661-6596}},
keywords = {{cytokines; HIV-2; host response; transcriptional regulation; viral pathogenesis; Vpx}},
language = {{eng}},
number = {{8}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx}},
url = {{http://dx.doi.org/10.3390/ijms26083460}},
doi = {{10.3390/ijms26083460}},
volume = {{26}},
year = {{2025}},
}