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Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus

Positions of the predicted HMGA1 binding sites at HIV-1 5’-LTR. Positionsof the 5’-LTR regions are specified: U3 (nucleotides 1–455), R(456–552), and U5 (553–634). Nucleotides are counted from thebeginning of the genome. The major regulatory regions of 5’-LTR areshown. +1 – counting from the transcription initiation site denoted by anarrow. HMGA1 binding sites determined in [69] are shown. The positions of nucleosomes on the HIV-1promoter are shown below; three sites of binding to the AP-1 transcriptionfactor are specified.
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Figure 7: Positions of the predicted HMGA1 binding sites at HIV-1 5’-LTR. Positionsof the 5’-LTR regions are specified: U3 (nucleotides 1–455), R(456–552), and U5 (553–634). Nucleotides are counted from thebeginning of the genome. The major regulatory regions of 5’-LTR areshown. +1 – counting from the transcription initiation site denoted by anarrow. HMGA1 binding sites determined in [69] are shown. The positions of nucleosomes on the HIV-1promoter are shown below; three sites of binding to the AP-1 transcriptionfactor are specified.

Mentions: Putative HMGA1 binding sites have been detected by DNase I footprinting in the-187/+230 region within HIV-1 LTR (R1–R5in Fig. 7)[69]. The interplay between HMGA1 andthe transcription factor AP-1 has also been studied: they were found to share abinding site (R5in Fig. 7).This site resides at the borderof the repressive nucleosome nuc-1, which exists in the provirus near thetranscription initiation site in the latent phase and degrades aftertranscription of the viral genome is activated(Fig. 7). HMGA1was found to facilitate binding of AP-1, an important inducible HIV- 1transcription activator, to viral DNA in response to external stimuliactivating viral expression. HMGA1 is possibly involved in the reorganizationof nuc-1 by competing for this site and making it free for AP-1. Hence, it hasbeen suggested that HMGA1 can positively regulate HIV-1 transcription[69].


Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

Positions of the predicted HMGA1 binding sites at HIV-1 5’-LTR. Positionsof the 5’-LTR regions are specified: U3 (nucleotides 1–455), R(456–552), and U5 (553–634). Nucleotides are counted from thebeginning of the genome. The major regulatory regions of 5’-LTR areshown. +1 – counting from the transcription initiation site denoted by anarrow. HMGA1 binding sites determined in [69] are shown. The positions of nucleosomes on the HIV-1promoter are shown below; three sites of binding to the AP-1 transcriptionfactor are specified.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837570&req=5

Figure 7: Positions of the predicted HMGA1 binding sites at HIV-1 5’-LTR. Positionsof the 5’-LTR regions are specified: U3 (nucleotides 1–455), R(456–552), and U5 (553–634). Nucleotides are counted from thebeginning of the genome. The major regulatory regions of 5’-LTR areshown. +1 – counting from the transcription initiation site denoted by anarrow. HMGA1 binding sites determined in [69] are shown. The positions of nucleosomes on the HIV-1promoter are shown below; three sites of binding to the AP-1 transcriptionfactor are specified.
Mentions: Putative HMGA1 binding sites have been detected by DNase I footprinting in the-187/+230 region within HIV-1 LTR (R1–R5in Fig. 7)[69]. The interplay between HMGA1 andthe transcription factor AP-1 has also been studied: they were found to share abinding site (R5in Fig. 7).This site resides at the borderof the repressive nucleosome nuc-1, which exists in the provirus near thetranscription initiation site in the latent phase and degrades aftertranscription of the viral genome is activated(Fig. 7). HMGA1was found to facilitate binding of AP-1, an important inducible HIV- 1transcription activator, to viral DNA in response to external stimuliactivating viral expression. HMGA1 is possibly involved in the reorganizationof nuc-1 by competing for this site and making it free for AP-1. Hence, it hasbeen suggested that HMGA1 can positively regulate HIV-1 transcription[69].

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus