title: Stability of HIV-1 subtype B and C Tat is associated with variation in the carboxyl-terminal region.
abstract: The multifunctional trans-activator Tat is an essential regulatory protein for HIV-1 replication and is characterized by high sequence diversity. Numerous experimental studies have examined Tat in HIV-1 subtype B, but research on subtype C Tat is lacking, despite the high prevalence of infections caused by subtype C worldwide. We hypothesized that amino acid differences contribute to functional differences among Tat proteins. In the present study, we found that subtype B NL4-3 Tat and subtype C isolate HIV1084i Tat exhibited differences in stability by overexpressing the fusion protein Tat-Flag. In addition, 1084i Tat can activate LTR and NF-κB more efficiently than NL4-3 Tat. In analyses of the activities of the truncated forms of Tat, we found that the carboxyl-terminal region of Tat regulates its stability and transactivity. According to our results, we speculated that the differences in stability between B-Tat and C-Tat result in differences in transactivation ability.
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, 300071, China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, 300071, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Qian
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, 300071, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, 300071, China.
authors.forename: Di
authors.initials: D
authors.lastname: Qi
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, 300071, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, 300071, China. kongxh@nankai.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Kong
mesh_terms: D019943:Amino Acid Substitution; D057809:HEK293 Cells; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: NF-κB activation; Tat; carboxyl-terminal region; stability; subtype B/C; transactivation