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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

Scheme of the HIV-1 genome and position of the Ku-binding site in 5’-LTR.A – positions of the 5’-LTR regions are specified:U3 (nucleotides 1–455), R (456–552), and U5 (553–638)(counting from the beginning of the genome). The major regulatory regions of5’-LTR are shown. +1 – counting from the transcription initiationsite denoted by an arrow. The Ku-binding site predicted in [6] is shown. B –alignment between the putative Ku-binding sites in the NRE-1 region of HIV-1and MMTV, as well as some other sequences similar to MMTV NRE-1 [6].
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Figure 5: Scheme of the HIV-1 genome and position of the Ku-binding site in 5’-LTR.A – positions of the 5’-LTR regions are specified:U3 (nucleotides 1–455), R (456–552), and U5 (553–638)(counting from the beginning of the genome). The major regulatory regions of5’-LTR are shown. +1 – counting from the transcription initiationsite denoted by an arrow. The Ku-binding site predicted in [6] is shown. B –alignment between the putative Ku-binding sites in the NRE-1 region of HIV-1and MMTV, as well as some other sequences similar to MMTV NRE-1 [6].

Mentions: Taking into account that Ku has a negative effect on transcription from otherretroviral promoters (MMTV, HTLV-1) [32,33], L. Jeanson and J.F. Mouscadet[6] searched for the Ku-binding site inthe HIV-1 LTR and detected a motif (-217/-197) in the NRE-1 region that wasrather similar to the Ku-binding site in MMTV NRE-1(Fig. 5)[6]. Several variants of Ku-mediatedrepression of HIV-1 transcription were proposed. Considering the fact that Kucan bind to the Oct-1 and Oct-2 transcription factors[36], which repress both the basal andTat-activated transcription of HIV-1, it was hypothesized that binding of Ku in themodulatory region(Fig. 5A)facilitates recruitment of these factors to the HIV-1 promoter[6]. It isalso possible that Ku can be involved in the regulation of the chromatinstructure. NRE-1 contains a nuclear matrix binding site[60] overlapping with the predicted Ku-binding site. Theinterplay between Ku and the nuclear matrix in this region presumably impedesNF-κB-activated transcription.


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

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

Scheme of the HIV-1 genome and position of the Ku-binding site in 5’-LTR.A – positions of the 5’-LTR regions are specified:U3 (nucleotides 1–455), R (456–552), and U5 (553–638)(counting from the beginning of the genome). The major regulatory regions of5’-LTR are shown. +1 – counting from the transcription initiationsite denoted by an arrow. The Ku-binding site predicted in [6] is shown. B –alignment between the putative Ku-binding sites in the NRE-1 region of HIV-1and MMTV, as well as some other sequences similar to MMTV NRE-1 [6].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Scheme of the HIV-1 genome and position of the Ku-binding site in 5’-LTR.A – positions of the 5’-LTR regions are specified:U3 (nucleotides 1–455), R (456–552), and U5 (553–638)(counting from the beginning of the genome). The major regulatory regions of5’-LTR are shown. +1 – counting from the transcription initiationsite denoted by an arrow. The Ku-binding site predicted in [6] is shown. B –alignment between the putative Ku-binding sites in the NRE-1 region of HIV-1and MMTV, as well as some other sequences similar to MMTV NRE-1 [6].
Mentions: Taking into account that Ku has a negative effect on transcription from otherretroviral promoters (MMTV, HTLV-1) [32,33], L. Jeanson and J.F. Mouscadet[6] searched for the Ku-binding site inthe HIV-1 LTR and detected a motif (-217/-197) in the NRE-1 region that wasrather similar to the Ku-binding site in MMTV NRE-1(Fig. 5)[6]. Several variants of Ku-mediatedrepression of HIV-1 transcription were proposed. Considering the fact that Kucan bind to the Oct-1 and Oct-2 transcription factors[36], which repress both the basal andTat-activated transcription of HIV-1, it was hypothesized that binding of Ku in themodulatory region(Fig. 5A)facilitates recruitment of these factors to the HIV-1 promoter[6]. It isalso possible that Ku can be involved in the regulation of the chromatinstructure. NRE-1 contains a nuclear matrix binding site[60] overlapping with the predicted Ku-binding site. Theinterplay between Ku and the nuclear matrix in this region presumably impedesNF-κB-activated transcription.

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