Abstract
Cellular tRNA(Lys-3) serves as the primer for reverse transcription of human immunodeficiency virus, type 1 (HIV-1), tRNA(Lys-3) interacts directly with HIV-1 reverse transcriptase, is packaged into vital particles and anneals to the primer-binding site (PBS) of the HIV-1 genome to initiate reverse transcription. Therefore, the priming step of reverse transcription is a potential target for antiviral strategies. We have developed a mutant tRNA(Lys-3) derivative with mutations in the PBS-binding region such that priming specificity was re-directed to the highly conserved TAR stem-loop region. This mutant tRNA retains high-affinity binding to HIV-1 reverse transcriptase, viral encapsidation, and is able to prime at both the targeted TAR sequence and at the viral PBS. Constitutive expression of mutant tRNA in T-cells results in marked inhibition of HIV-1 replication, as determined by measurements of viral infectivity, syncytium formation, and p24 production. Inhibition of retroviral replication through interference with the normal process of priming constitutes a new anti-retroviral approach and also provides a novel tool for dissecting molecular aspects of priming.
| Original language | English |
|---|---|
| Pages (from-to) | 14523-14531 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 272 |
| Issue number | 23 |
| DOIs | |
| State | Published - Jun 6 1997 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Inhibition of HIV-1 replication using a mutated tRNA(Lys-3) primer. / Lu, Yuanan; Planelles, Vicente; Li, Xinqiang; Palaniappan, Chockalingam; Day, Brian; Challita-Eid, Pia; Amado, Rafael; Stephens, Dennis; Kohn, Donald B.; Bakker, Andreas; Fay, Philip; Bambara, Robert A.; Rosenblatt, Joseph D.
In: Journal of Biological Chemistry, Vol. 272, No. 23, 06.06.1997, p. 14523-14531.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of HIV-1 replication using a mutated tRNA(Lys-3) primer
AU - Lu, Yuanan
AU - Planelles, Vicente
AU - Li, Xinqiang
AU - Palaniappan, Chockalingam
AU - Day, Brian
AU - Challita-Eid, Pia
AU - Amado, Rafael
AU - Stephens, Dennis
AU - Kohn, Donald B.
AU - Bakker, Andreas
AU - Fay, Philip
AU - Bambara, Robert A.
AU - Rosenblatt, Joseph D
PY - 1997/6/6
Y1 - 1997/6/6
N2 - Cellular tRNA(Lys-3) serves as the primer for reverse transcription of human immunodeficiency virus, type 1 (HIV-1), tRNA(Lys-3) interacts directly with HIV-1 reverse transcriptase, is packaged into vital particles and anneals to the primer-binding site (PBS) of the HIV-1 genome to initiate reverse transcription. Therefore, the priming step of reverse transcription is a potential target for antiviral strategies. We have developed a mutant tRNA(Lys-3) derivative with mutations in the PBS-binding region such that priming specificity was re-directed to the highly conserved TAR stem-loop region. This mutant tRNA retains high-affinity binding to HIV-1 reverse transcriptase, viral encapsidation, and is able to prime at both the targeted TAR sequence and at the viral PBS. Constitutive expression of mutant tRNA in T-cells results in marked inhibition of HIV-1 replication, as determined by measurements of viral infectivity, syncytium formation, and p24 production. Inhibition of retroviral replication through interference with the normal process of priming constitutes a new anti-retroviral approach and also provides a novel tool for dissecting molecular aspects of priming.
AB - Cellular tRNA(Lys-3) serves as the primer for reverse transcription of human immunodeficiency virus, type 1 (HIV-1), tRNA(Lys-3) interacts directly with HIV-1 reverse transcriptase, is packaged into vital particles and anneals to the primer-binding site (PBS) of the HIV-1 genome to initiate reverse transcription. Therefore, the priming step of reverse transcription is a potential target for antiviral strategies. We have developed a mutant tRNA(Lys-3) derivative with mutations in the PBS-binding region such that priming specificity was re-directed to the highly conserved TAR stem-loop region. This mutant tRNA retains high-affinity binding to HIV-1 reverse transcriptase, viral encapsidation, and is able to prime at both the targeted TAR sequence and at the viral PBS. Constitutive expression of mutant tRNA in T-cells results in marked inhibition of HIV-1 replication, as determined by measurements of viral infectivity, syncytium formation, and p24 production. Inhibition of retroviral replication through interference with the normal process of priming constitutes a new anti-retroviral approach and also provides a novel tool for dissecting molecular aspects of priming.
UR - http://www.scopus.com/inward/record.url?scp=12644296997&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12644296997&partnerID=8YFLogxK
U2 - 10.1074/jbc.272.23.14523
DO - 10.1074/jbc.272.23.14523
M3 - Article
VL - 272
SP - 14523
EP - 14531
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 23
ER -