scholarly journals Annealing to sequences within the primer binding site loop promotes an HIV-1 RNA conformation favoring RNA dimerization and packaging

RNA ◽  
2013 ◽  
Vol 19 (10) ◽  
pp. 1384-1393 ◽  
Author(s):  
E. Seif ◽  
M. Niu ◽  
L. Kleiman
Keyword(s):  
Binding Site ◽  
Primer Binding Site ◽  
Rna Dimerization ◽  
Rna Conformation ◽  
Hiv 1

scholarly journals Mutations in the U5 Region Adjacent to the Primer Binding Site Affect tRNA Cleavage by Human Immunodeficiency Virus Type 1 Reverse Transcriptase In Vivo

2007 ◽  
Vol 82 (2) ◽  
pp. 719-727 ◽  
Author(s):  
Jangsuk Oh ◽  
Mary Jane McWilliams ◽  
John G. Julias ◽  
Stephen H. Hughes
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Binding Site ◽  
Rnase H ◽  
Primer Binding Site ◽  
Cleavage Specificity ◽  
Immunodeficiency Virus ◽  
Trna Primer ◽  
Hiv 1

ABSTRACT In retroviruses, the first nucleotide added to the tRNA primer defines the end of the U5 region in the right long terminal repeat, and the subsequent removal of this tRNA primer by RNase H exactly defines the U5 end of the linear double-stranded DNA. In most retroviruses, the entire tRNA is removed by RNase H cleavage at the RNA/DNA junction. However, the RNase H domain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase cleaves the tRNA 1 nucleotide from the RNA/DNA junction at the U5/primer binding site (PBS) junction, which leaves an rA residue at the U5 terminus. We made sequence changes at the end of the U5 region adjacent to the PBS in HIV-1 to determine whether such changes affect the specificity of tRNA primer cleavage by RNase H. In some of the mutants, RNase H usually removed the entire tRNA, showing that the cleavage specificity was shifted by 1 nucleotide. This result suggests that the tRNA cleavage specificity of the HIV-1 RNase domain H depends on sequences in U5.

How the HIV-1 Nucleocapsid Protein Binds and Destabilises the (−)Primer Binding Site During Reverse Transcription

2008 ◽  
Vol 383 (5) ◽  
pp. 1112-1128 ◽  
Author(s):  
Sarah Bourbigot ◽  
Nick Ramalanjaona ◽  
Christian Boudier ◽  
Gilmar F.J. Salgado ◽  
Bernard P. Roques ◽  
...  
Keyword(s):  
Binding Site ◽  
Reverse Transcription ◽  
Nucleocapsid Protein ◽  
Primer Binding Site ◽  
Hiv 1

scholarly journals Insights into the Interaction between tRNA and Primer Binding Site from Characterization of a Unique HIV-1 Virus Which Stably Maintains Dual PBS Complementary to tRNAGlyand tRNAHis

Virology ◽  
1997 ◽  
Vol 238 (2) ◽  
pp. 273-282 ◽  
Author(s):  
Yun Li ◽  
Zhijun Zhang ◽  
Sang-Moo Kang ◽  
James L. Buescher ◽  
Casey D. Morrow
Keyword(s):  
Binding Site ◽  
Primer Binding Site ◽  
Hiv 1

Mechanistic Insights into the Kinetics of HIV-1 Nucleocapsid Protein-facilitated tRNA Annealing to the Primer Binding Site

2004 ◽  
Vol 337 (4) ◽  
pp. 951-968 ◽  
Author(s):  
Michele R.S. Hargittai ◽  
Robert J. Gorelick ◽  
Ioulia Rouzina ◽  
Karin Musier-Forsyth
Keyword(s):  
Binding Site ◽  
Nucleocapsid Protein ◽  
Primer Binding Site ◽  
Kinetics Of ◽  
Hiv 1

scholarly journals A Nucleotide Substitution in the tRNALys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

2002 ◽  
Vol 76 (11) ◽  
pp. 5803-5806 ◽  
Author(s):  
Kelly Soderberg ◽  
Lynn Denekamp ◽  
Sarah Nikiforow ◽  
Karen Sautter ◽  
Ronald C. Desrosiers ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Binding Site ◽  
Simian Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Nucleotide Substitution ◽  
Primer Binding Site ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A recombinant simian immunodeficiency virus (SIV) derived from strain 239 (SIVmac239) with reverse transcriptase (RT) sequences from human immunodeficiency virus type 1 (HIV-1) strain HXB2 was severely impaired for replication. Detectable p27Gag levels were not observed until day 65 and peak p27Gag levels were not reached until day 75 after transfection of CEMx174 cells with the recombinant DNA. Sequences from the latter time point did not contain amino acid substitutions in HIV-1 RT; however, a single nucleotide substitution (thymine to cytosine) was found at position eight of the SIV primer binding site. We engineered an RT/SHIV genome with the thymine-to-cytosine substitution, called RT/SHIV/TC, and observed dramatically faster replication kinetics than were observed with the parental RT/SHIV from which this variant was derived. RT/SHIV/TC provides an improved system for study of the impact of drug resistance mutations in HIV-1 RT in a relevant animal model.

scholarly journals Short- and long-range interactions in the HIV-1 5’UTR regulate genome dimerization and packaging

2021 ◽  
Author(s):  
Redmond Smyth ◽  
Liqing Ye ◽  
Anne-Sophie Gribling ◽  
Patrick Bohn ◽  
Anuja Kibe ◽  
...  
Keyword(s):  
Life Cycle ◽  
Rna Structure ◽  
Mechanistic Explanation ◽  
Primer Binding Site ◽  
Rna Dimerization ◽  
Long Range Interactions ◽  
Retroviral Replication ◽  
Genome Dimerization ◽  
Late Stages ◽  
Hiv 1

Abstract Genome dimerization is a conserved feature of retroviral replication and a critical step in the HIV-1 life cycle, but how it is regulated is incompletely understood. Here, we developed FARS-seq (Functional Analysis of RNA Structure) to comprehensively identify sequences and structures within the HIV-1 5’UTR influencing dimerization. We found nucleotides important for dimerization throughout the HIV-1 5’UTR and identified distinct structural conformations in monomeric and dimeric RNA. The dimer displayed TAR, PolyA, PBS, and SL1-SL3 as stem-loops. In the monomer, SL1 was dramatically reconfigured into long- and short-range base-pairings with polyA and PBS, respectively. The polyA-SL1 interaction disrupts the major packaging motifs, and the PBS-SL1 interaction functionally couples the primer binding site with dimerization and Pr55Gag binding. Altogether, our data provide insights into late stages of HIV-1 life cycle and a mechanistic explanation for the link between RNA dimerization and packaging.

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 Replication with Artificial Transcription Factors Targeting the Highly Conserved Primer-Binding Site

2006 ◽  
Vol 80 (6) ◽  
pp. 2873-2883 ◽  
Author(s):  
Scott R. Eberhardy ◽  
Joao Goncalves ◽  
Sofia Coelho ◽  
David J. Segal ◽  
Ben Berkhout ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transcription Factors ◽  
Viral Replication ◽  
Binding Site ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Primer Binding Site ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) primer-binding site (PBS) is a highly conserved region in the HIV genome and represents an attractive target for the development of new anti-HIV therapies. In this study, we designed four artificial zinc finger transcription factors to bind at or adjacent to the PBS and repress transcription from the HIV-1 long terminal repeat (LTR). These proteins bound to the LTR in vivo, as demonstrated by the chromatin immunoprecipitation assay. In transient reporter assays, three of the four proteins repressed transcription of a reporter driven by the HIV-1 LTR. Only one of these proteins, however, designated KRAB-PBS2, was able to prevent virus production when transduced into primary lymphocytes. We observed >90% inhibition of viral replication over the course of several weeks compared to untransduced cells, and no significant cytotoxicity was observed. Long-term exposure of HIV-1 to KRAB-PBS2 induced mutations in the HIV-1 PBS that reduced the effectiveness of the repressor, but these mutations also resulted in decreased rates of viral replication. These results show that KRAB-PBS2 has the potential to be used in antiviral therapy for AIDS patients and might complement other gene-based strategies.

Sign in / Sign up

Export Citation Format

Share Document