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001-es BibID:	BIBFORM103432
035-os BibID:	(cikkazonosító)1888 (WOS)000856936200001 (Scopus)85138336056
Első szerző:	Mótyán János András (biokémikus, molekuláris biológus)
Cím:	Different Mutation Tolerance of Lentiviral (HIV-1) and Deltaretroviral (BLV and HTLV) Protease Precursors / Mótyán János András, Kassay Norbert, Matúz Krisztina, Tőzsér József
Dátum:	2022
ISSN:	1999-4915
Megjegyzések:	The bovine leukemia virus (BLV) and the human T-lymphothropic viruses (HTLVs) are members of the deltaretrovirus genus of Retroviridae family. An essential event of the retroviral life cycle is the processing of the polyproteins by the viral protease (PR); consequently, these enzymes became important therapeutic targets of the anti-retroviral drugs. As compared to human immunodeficiency viruses (HIVs), the deltaretroviruses have a different replication strategy, as they replicate predominantly in the DNA form, by forcing the infected cell to divide, unlike HIV-1, which replicates mainly by producing a vast number of progeny virions and by reinfection. Due to bypassing the error-prone reverse transcription step of replication, the PRs of deltaretroviruses did not undergo such extensive evolution as HIV PRs and remained more highly conserved. In this work, we studied the abilities of wild-type and modified BLV, HTLV (type 1, 2 and 3), and HIV-1 PRs (fused to an N-terminal MBP tag) for self-processing. We designed a cleavage site mutant MBP-fused BLV PR precursor as well, this recombinant enzyme was unable for self-proteolysis, the MBP fusion tag decreased its catalytic efficiency but showed an unusually low Ki for the IB-268 protease inhibitor. Our results show that the HTLV and BLV deltaretrovirus PRs exhibit lower mutation tolerance as compared to HIV-1 PR, and are less likely to retain their activity upon point mutations at various positions, indicating a higher flexibility of HIV-1 PR in tolerating mutations under selective pressure.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk human T-lymphotropic virus HTLV BLV retroviral protease autoproteolysis retrovirus human immunodeficiency virus HIV-1 protease bovine leukemia virus
Megjelenés:	Viruses-Basel. - 14 : 9 (2022), p. 1-17. -
További szerzők:	Kassay Norbert (1988-) (biotechnológus) Matúz Krisztina (1980-) (vegyész, biokémikus) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész)
Pályázati támogatás:	TKP2021-EGA-20 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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