NDLI: Functional Characterization of Chimeric Reverse Transcriptases with Polypeptide Subunits of Highly Divergent HIV-1 Group M and O Strains

Content Provider	Journal of Biological Chemistry (JBC)
Author	Menéndez-Arias, Luis Abraha, Awet Quiñones-Mateu, Miguel E. Mas, Antonio Camarasa, Marı́a-José Arts, Eric J.
Abstract	Human immunodeficiency virus (HIV)-1 strains have been divided into three groups: main (M), outlier (O), and non-M non-O (N). Biochemical analyses of HIV-1 reverse transcriptase (RT) have been performed predominantly with enzymes derived from HIV-1 group M:subtype B laboratory strains. This study was designed to optimize the expression and to characterize the enzymatic properties of HIV-1 group O RTs as well as chimeric RTs composed of group M and O p66 and p51 subunits. The DNA-dependent DNA polymerase activity on a short heteropolymeric template-primer was similar with all enzymes,i.e. the HIV-1 group O and M and chimeric RTs. Our data revealed that the 51-kDa subunit in the chimeric heterodimer p66M:B/p51O confers increased heterodimer stability and partial resistance to non-nucleoside RT inhibitors. Chimeric RTs (p66M:B/p51O and p66O/p51M:B) were unable to initiate reverse transcription from tRNA using HIV-1 group O or group M:subtype B RNA templates. In contrast, HIV-1 group O and M RTs supported (−)-strand DNA synthesis from tRNA hybridized to any of their corresponding HIV-1 RNA templates. HIV-2 RT could not initiate reverse transcription on tRNA -primed HIV-1 genomic RNA. These findings suggest that the initiation event is conserved between HIV-1 groups, but not HIV types.
Related Links	http://www.jbc.org/content/276/29/27470.abstract
Ending Page	27479
Starting Page	27470
Page Count	10
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	29
Volume Number	276
DOI	10.1074/jbc.M104342200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2001-07-20
Access Restriction	Open
Subject Keyword	Human immunodeficiency virus (HIV) Reverse transcriptase (RT) Non-nucleoside reverse transcriptase inhibitor (NNRTI) Group M:subtype B (M:B) Polymerase chain reaction (PCR) Dithiothreitol (DTT) [2′,5′-bis-O-(tert-butyldimethylsilyl)- β-d-ribofuranosyl]-3′-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide) (TSAO) [1-[2′,5′-bis-O-(tert-butyldimethylsilyl)-β-d-ribofuranosyl]-thymine]-3′-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide) (TSAO-T) [1-[2′,5′-bis-O-(tert-butyldimethylsilyl)-β-d-ribofuranosyl]-N3-methylthymine]-3′-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide) (TSAO-m3T) Unique 5′ (U5) Primer-binding site (pbs) Feline immunodeficiency virus (FIV) Tetrahydroimidazo [4,5,1-jk][1,4]benzodiazepin-2(IH)-thione (TIBO) ENZYME CATALYSIS AND REGULATION
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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Mutational Analysis of Tyr-318 within the Non-nucleoside Reverse Transcriptase Inhibitor Binding Pocket of Human Immunodeficiency Virus Type I Reverse Transcriptase

Kinetics of inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase by the novel HIV-1-specific nucleoside analogue [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5 "- (4"-amino-1",2"-oxathiole-2",2"-dioxide)thymine (TSAO-T).

2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2'-dioxide)pyrimidine (TSAO) nucleoside analogues: highlyselective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase.

Resistance of HIV-1 reverse transcriptase against [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2''-dioxide)] (TSAO) derivatives is determined by the mutation Glu138-->Lys on the p51 subunit.

Identification of a putative binding site for [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)thymine (TSAO) derivatives at the p51-p66 interface of HIV-1 reverse transcriptase.

[2',5'-Bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives of purine and pyrimidinenucleosides as potent and selective inhibitors of human immunodeficiency virus type 1.

Functional Characterization of Chimeric Reverse Transcriptases with Polypeptide Subunits of Highly Divergent HIV-1 Group M and O Strains

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Functional Characterization of Chimeric Reverse Transcriptases with Polypeptide Subunits of Highly Divergent HIV-1 Group M and O Strains