The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid

Retrovirology
Jing ZhouChristopher Aiken

Abstract

Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB) specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast, SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB, we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4+ T cells. Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to DSB, but the mutant virus replicated with reduced efficiency. Conversely, replication of an SIV mutant containing three amino acid substitutions in the CA-SP1 cleavage site was highly sensitive to DSB, and the mutations resulted in delayed cleavage of the CA-SP1 junction in the p...Continue Reading

References

Jun 7, 1985·Science·M D DanielR C Desrosiers
Aug 1, 1997·Methods : a Companion to Methods in Enzymology·K Wehrly, B Chesebro
Oct 24, 2003·Proceedings of the National Academy of Sciences of the United States of America·F LiC T Wild

❮ Previous
Next ❯

Citations

Mar 12, 2011·The Protein Journal·Zhigang LiuLadislau C Kovari
Jun 17, 2009·Journal of Medicinal Chemistry·Zhao DangLi Huang
Oct 7, 2009·Antimicrobial Agents and Chemotherapy·Wade S BlairScott L Butler
Mar 24, 2010·Antimicrobial Agents and Chemotherapy·Nicolas A MargotMichael D Miller
Nov 26, 2010·Journal of Virology·Paul W KellerAlasdair C Steven
Sep 7, 2004·Retrovirology·Kuan-Teh Jeang
Dec 17, 2009·Retrovirology·Kuan-Teh Jeang
Apr 22, 2009·AIDS·Brij B SaxenaSidney Lerner
Jul 12, 2005·Expert Opinion on Investigational Drugs·Donglei YuKuo-Hsiung Lee
Jul 16, 2016·ELife·Jonathan M WagnerOwen Pornillos
Aug 14, 2012·Molecular Biology International·Catherine S Adamson
Nov 26, 2008·Antiviral Chemistry & Chemotherapy·David E MartinGraham P Allaway
Jul 20, 2016·Antimicrobial Agents and Chemotherapy·Zachary S MartinezManuel Llano
Aug 5, 2006·Medicinal Research Reviews·Donglei YuKuo-Hsiung Lee
Jun 19, 2009·Expert Opinion on Therapeutic Targets·Catherine S AdamsonEric O Freed
Aug 30, 2020·Viruses·Alex B Kleinpeter, Eric O Freed
Oct 28, 2005·The Journal of Biological Chemistry·Jing ZhouChristopher Aiken
Apr 17, 2018·Biochemical and Biophysical Research Communications·Jasmine PhillipsTakayuki Nitta
Jun 12, 2019·Current Opinion in Virology·Owen Pornillos, Barbie K Ganser-Pornillos

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
transfection
PCR

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.