title: The variances of Sp1 and NF-κB elements correlate with the greater capacity of Chinese HIV-1 B'-LTR for driving gene expression.
abstract: The 5' end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an essential role in driving viral gene transcription. Manipulation of HIV-1 LTR provides a potential therapeutic strategy for suppressing viral gene expression or excising integrated provirus. Subtype-specific genetic diversity in the LTR region has been observed. The minor variance of LTR, particularly in the transcription factor binding sites, can have a profound impact on its activity. However, the LTR profiles from major endemic Chinese subtypes are not well characterized. Here, by characterizing the sequences and functions of LTRs from endemic Chinese HIV-1 subtypes, we showed that nucleotide variances of Sp1 core promoter and NF-κB element are associated with varied LTR capacity for driving viral gene transcription. The greater responsiveness of Chinese HIV-1 B'-LTR for driving viral gene transcription upon stimulation is associated with an increased level of viral reactivation. Moreover, we demonstrated that the introduction of CRISPR/dead Cas9 targeting Sp1 or NF-κB element suppressed viral gene expression. Taken together, our study characterized LTRs from endemic HIV-1 subtypes in China and suggests a potential target for the suppression of viral gene expression and a novel strategy that facilitates the accomplishment of a functional cure.
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Di
authors.initials: D
authors.lastname: Qu
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Key laboratory of Prevention and Treatment with Traditional Chinese Medicine on Viral Infection Disease, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Sang
authors.affiliation: Key laboratory of Prevention and Treatment with Traditional Chinese Medicine on Viral Infection Disease, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key laboratory of Prevention and Treatment with Traditional Chinese Medicine on Viral Infection Disease, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Jiang
authors.affiliation: Key laboratory of Prevention and Treatment with Traditional Chinese Medicine on Viral Infection Disease, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Li-Ran
authors.initials: LR
authors.lastname: Xu
authors.affiliation: Key laboratory of Prevention and Treatment with Traditional Chinese Medicine on Viral Infection Disease, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Guo
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chiyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
mesh_terms: D002681:China; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D057809:HEK293 Cells; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human