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001-es BibID:	BIBFORM104263
035-os BibID:	(Scopus)85141175162 (WOS)000888173300001 (PubMed)36341352
Első szerző:	Miltner Noémi (molekuláris biológus)
Cím:	Early suppression of antiviral host response and protocadherins by SARS-CoV-2 Spike protein in THP-1-derived macrophage-like cells / Miltner Noémi, Linkner Tamás Richárd, Ambrus Viktor, Al-Muffti Aya S., Ahmad Hala, Mótyán János András, Benkő Szilvia, Tőzsér József, Mahdi Mohamed
Dátum:	2022
ISSN:	1664-3224
Megjegyzések:	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19). The spike protein (S) of SARS-CoV-2 plays a crucial role in mediating viral infectivity; hence, in an extensive effort to curb the pandemic, many urgently approved vaccines rely on the expression of the S protein, aiming to induce a humoral and cellular response to protect against the infection. Given the very limited information about the effects of intracellular expression of the S protein in host cells, we aimed to characterize the early cellular transcriptomic changes induced by expression of the S protein in THP-1-derived macrophage-like cells. Results showed that a wide variety of genes were differentially expressed, products of which are mainly involved in cell adhesion, homeostasis, and most notably, antiviral and immune responses, depicted by significant downregulation of protocadherins and type I alpha interferons (IFNAs). While initially, the levels of IFNAs were higher in the medium of S protein expressing cells, the downregulation observed on the transcriptomic level might have been reflected by no further increase of IFNA cytokines beyond the 5 h time-point, compared to the mock control. Our study highlights the intrinsic pathogenic role of the S protein and sheds some light on the potential drawbacks of its utilization in the context of vaccination strategies.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk SARS-CoV-2 coronavirus COVID-19 spike protein transcriptomics virology
Megjelenés:	Frontiers in Immunology. - 13 (2022), p. 999233. -
További szerzők:	Linkner Tamás Richárd Ambrus Viktor Attila (1989-) (biotechnológus) Al-Muffti, Aya S. (1990-) Ahmad, Hala Mótyán János András (1981-) (biokémikus, molekuláris biológus) Benkő Szilvia (1973-) (molekuláris biológus) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Mahdi, Mohamed (1979-) (orvos, tudományos segédmunkatárs)
Pályázati támogatás:	TKP2021-EGA-20 Egyéb POST-COVID2021-16 Egyéb K131844 OTKA
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001-es BibID:	BIBFORM129863
035-os BibID:	(scopus)105003781418 (wos)001475447900001
Első szerző:	Szojka Zsófia (molekuláris biológus)
Cím:	Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx / Zsófia Ilona Szojka, Balázs Kunkli, Irene Wanjiru Kiarie, Tamás Richárd Linkner, Aya Shamal Al-Muffti, Hala Ahmad, Szilvia Benkő, Marianne Jansson, József Tőzsér, Mohamed Mahdi
Dátum:	2025
ISSN:	1661-6596 1422-0067
Megjegyzések:	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.
Tárgyszavak:	Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk HIV-2 Vpx host response viral pathogenesis transcriptional regulation cytokines
Megjelenés:	International Journal Of Molecular Sciences. - 26 : 8 (2025), p. 1-21. -
További szerzők:	Kunkli Balázs (1990-) (bioinformatikus, biokémikus) Kiarie, Irene Wanjiru Linkner Tamás Richárd Al-Muffti, Aya S. (1990-) Ahmad, Hala Benkő Szilvia (1973-) (molekuláris biológus) Jansson, Marianne Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Mahdi, Mohamed (1979-) (orvos, tudományos segédmunkatárs)
Pályázati támogatás:	TKP2021-EGA-20 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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