Leiherer, Andreas and Ludwig, Christine and Wagner, Ralf (2009) Uncoupling Human Immunodeficiency Virus Type 1 gag and pol Reading Frames: Role of the Transframe Protein p6*in Viral Replication. JOURNAL OF VIROLOGY, 83 (14). pp. 7210-7220. ISSN 0022-538X, 1098-5514
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Apart from its regulatory role in protease ( PR) activation, little is known about the function of the human immunodeficiency virus type 1 transframe protein p6* in the virus life cycle. p6* is located between the nucleocapsid and PR domains in the Gag-Pol polyprotein precursor and is cleaved by PR during viral maturation. We have recently reported that the central region of p6* can be extensively mutated without abolishing viral infectivity and replication in vitro. However, mutagenesis of the entire p6*-coding sequence in the proviral context is not feasible without affecting the superimposed frameshift signal or the overlapping p1-p6(gag) sequences. To overcome these limitations, we created a novel NL4-3-derived provirus by displacing the original frameshift signal to the 3' end of the gag gene, thereby uncoupling the p6* gene sequence from the p1-p6(gag) reading frame. The resulting virus (AL) proved to be replication competent in different cell cultures and thus represents an elegant tool for detailed analysis of p6* function. Hence, extensive deletions or substitutions were introduced into the p6* gene sequence of the AL provirus, and effects on particle release, protein processing, and viral infectivity were evaluated. Interestingly, neither the deletion of 63% of all p6* residues nor the partial substitution by a heterologous sequence affected virus growth and infectivity, suggesting that p6* is widely dispensable for viral in vitro replication. However, the insertion of a larger reporter sequence interfered with virus production and maturation, implying that the length or conformation of this spacer region might be critical for p6* function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIV-1 PROTEASE; CLEAVAGE SITES; CENTRAL REGION; P6 PROTEIN; PRECURSOR; POLYPROTEIN; RESIDUES; DOMAINS; INFECTIVITY; ACTIVATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Sep 2020 09:53 |
| Last Modified: | 10 Sep 2020 09:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28703 |
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