{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T08:55:34Z","timestamp":1780131334021,"version":"3.54.0"},"reference-count":78,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["150532"],"award-info":[{"award-number":["150532"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["K147109"],"award-info":[{"award-number":["K147109"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government of Hungary","award":["150532"],"award-info":[{"award-number":["150532"]}]},{"name":"Government of Hungary","award":["K147109"],"award-info":[{"award-number":["K147109"]}]},{"name":"Richter Gedeon Talentum PhD Excellence scholarship","award":["150532"],"award-info":[{"award-number":["150532"]}]},{"name":"Richter Gedeon Talentum PhD Excellence scholarship","award":["K147109"],"award-info":[{"award-number":["K147109"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats: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.<\/jats:p>","DOI":"10.3390\/ijms26083460","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T09:47:55Z","timestamp":1744105675000},"page":"3460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx"],"prefix":"10.3390","volume":"26","author":[{"given":"Zs\u00f3fia Ilona","family":"Szojka","sequence":"first","affiliation":[{"name":"Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Division of Medical Microbiology, Department of Laboratory Medicine, Lund University, Box 188, SE-221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-2792","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Kunkli","sequence":"additional","affiliation":[{"name":"Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene Wanjiru","family":"Kiarie","sequence":"additional","affiliation":[{"name":"Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s Rich\u00e1rd","family":"Linkner","sequence":"additional","affiliation":[{"name":"Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya Shamal","family":"Al-Muffti","sequence":"additional","affiliation":[{"name":"Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Laboratory of Inflammation-Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-6345","authenticated-orcid":false,"given":"Szilvia","family":"Benk\u0151","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation-Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Jansson","sequence":"additional","affiliation":[{"name":"Division of Medical Microbiology, Department of Laboratory Medicine, Lund University, Box 188, SE-221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-8729","authenticated-orcid":false,"given":"J\u00f3zsef","family":"T\u0151zs\u00e9r","sequence":"additional","affiliation":[{"name":"Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7959-5996","authenticated-orcid":false,"given":"Mohamed","family":"Mahdi","sequence":"additional","affiliation":[{"name":"Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5941","DOI":"10.1073\/pnas.85.16.5941","article-title":"Genetic variability between isolates of human immunodeficiency virus (HIV) type 2 is comparable to the variability among HIV type 1","volume":"85","author":"Zagury","year":"1988","journal-title":"Proc. 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