In vivo processing of Pr160gag-pol from human immunodeficiency virus type 1 (HIV) in acutely infected, cultured human T-lymphocytes
- PMID: 8553565
- DOI: 10.1006/viro.1995.0074
In vivo processing of Pr160gag-pol from human immunodeficiency virus type 1 (HIV) in acutely infected, cultured human T-lymphocytes
Abstract
The processing of the HIV-1 Pr160gag-pol precursor polyprotein was analyzed in freshly HIV-1-infected MT-4 cultured cells. Single intermediates of the processing cascade were characterized by immunoblotting using distinct antisera. A potent inhibitor of the HIV protease (PR), Ro 31-8959, was employed to block cleavage by the mature PR, thus allowing insights into initial stages of the gag-pol (auto)-catalytical processing. While most known gag-pol cleavages were blocked in the presence of the inhibitor, the cleavage site between the gag-NC and the pol-p6 domains was still cleaved even in presence of high amounts (1 microM) of inhibitor, leading to the accumulation of a novel 114-kDa polyprotein comprising p6-PR-RT-IN. In the absence of inhibitor no accumulation of p114 was observed. In inhibitor-treated, HIV-1-infected cells a p6-PR intermediate was also detected, indicating subsequent cleavage of the PR/RT scissile bond. These results demonstrate initial cleavage(s) of the gag-pol precursor hydrolyzed by a proteolytic activity different from the mature PR and indicate that p114 (p6-PR-RT-IN) and p6-PR intermediates could play an essential role in the PR activation process.
Similar articles
-
Natural variation in HIV-1 protease, Gag p7 and p6, and protease cleavage sites within gag/pol polyproteins: amino acid substitutions in the absence of protease inhibitors in mothers and children infected by human immunodeficiency virus type 1.Virology. 1996 May 15;219(2):407-16. doi: 10.1006/viro.1996.0266. Virology. 1996. PMID: 8638406
-
Naturally occurring amino acid polymorphisms in human immunodeficiency virus type 1 (HIV-1) Gag p7(NC) and the C-cleavage site impact Gag-Pol processing by HIV-1 protease.Virology. 2002 Jan 5;292(1):137-49. doi: 10.1006/viro.2001.1184. Virology. 2002. PMID: 11878916
-
Extensive regions of pol are required for efficient human immunodeficiency virus polyprotein processing and particle maturation.Virology. 1996 May 1;219(1):29-36. doi: 10.1006/viro.1996.0219. Virology. 1996. PMID: 8623542
-
Activation mechanism of pepsinogen as compared to the processing of HIV protease gag-pol precursor protein.Adv Exp Med Biol. 1998;436:245-52. doi: 10.1007/978-1-4615-5373-1_34. Adv Exp Med Biol. 1998. PMID: 9561226 Review. No abstract available.
-
Expression systems for retroviral proteases.Methods Enzymol. 1994;241:3-16. doi: 10.1016/0076-6879(94)41055-0. Methods Enzymol. 1994. PMID: 7854184 Review. No abstract available.
Cited by
-
A Direct Interaction with RNA Dramatically Enhances the Catalytic Activity of the HIV-1 Protease In Vitro.J Mol Biol. 2015 Jul 17;427(14):2360-78. doi: 10.1016/j.jmb.2015.05.007. Epub 2015 May 15. J Mol Biol. 2015. PMID: 25986307 Free PMC article.
-
Comparison of human immunodeficiency virus type 1 Pr55(Gag) and Pr160(Gag-pol) processing intermediates that accumulate in primary and transformed cells treated with peptidic and nonpeptidic protease inhibitors.Antimicrob Agents Chemother. 2000 May;44(5):1397-403. doi: 10.1128/AAC.44.5.1397-1403.2000. Antimicrob Agents Chemother. 2000. PMID: 10770790 Free PMC article.
-
Conformational Changes in HIV-1 Reverse Transcriptase that Facilitate Its Maturation.Structure. 2019 Oct 1;27(10):1581-1593.e3. doi: 10.1016/j.str.2019.08.004. Epub 2019 Aug 27. Structure. 2019. PMID: 31471129 Free PMC article.
-
The nucleocapsid region of human immunodeficiency virus type 1 Gag assists in the coordination of assembly and Gag processing: role for RNA-Gag binding in the early stages of assembly.J Virol. 2009 Aug;83(15):7718-27. doi: 10.1128/JVI.00099-09. Epub 2009 May 20. J Virol. 2009. PMID: 19457986 Free PMC article.
-
Class II transactivator (CIITA) enhances cytoplasmic processing of HIV-1 Pr55Gag.PLoS One. 2010 Jun 24;5(6):e11304. doi: 10.1371/journal.pone.0011304. PLoS One. 2010. PMID: 20585587 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
