Generation and characterization of a human immunodeficiency virus type 1 (HIV-1) mutant resistant to an HIV-1 protease inhibitor.
| References: | Proc Natl Acad Sci U S A. 1989 Jul;86(13):4803-7. (PMID: 2472634) Nature. 1990 Jan 4;343(6253):90-2. (PMID: 1688646) Science. 1990 Jan 26;247(4941):454-6. (PMID: 2405486) AIDS. 1989 Dec;3(12):777-84. (PMID: 2483618) Science. 1990 Apr 20;248(4953):358-61. (PMID: 2183354) Science. 1990 Sep 28;249(4976):1533-44. (PMID: 1699273) Virology. 1990 Nov;179(1):508-11. (PMID: 2219737) J Immunol. 1990 Nov 15;145(10):3240-6. (PMID: 1700002) Science. 1985 Aug 9;229(4713):563-6. (PMID: 2992081) Cancer Lett. 1986 Mar;30(3):299-310. (PMID: 2421869) J Virol. 1986 Aug;59(2):284-91. (PMID: 3016298) Jpn J Cancer Res. 1987 Mar;78(3):235-41. (PMID: 3106279) Proc Natl Acad Sci U S A. 1988 Jul;85(13):4686-90. (PMID: 3290901) J Virol. 1988 Nov;62(11):3993-4002. (PMID: 3262776) J Virol Methods. 1988 Aug;20(4):309-21. (PMID: 2460479) J Virol. 1991 Sep;65(9):4887-92. (PMID: 1714522) J Infect Dis. 1991 Dec;164(6):1066-74. (PMID: 1955709) J Infect Dis. 1991 Dec;164(6):1075-81. (PMID: 1720152) J Virol. 1992 Jan;66(1):12-9. (PMID: 1727474) Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11241-5. (PMID: 1722324) Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11363-7. (PMID: 1722328) Virus Genes. 1991 Jul;5(3):189-202. (PMID: 1722929) Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7543-7. (PMID: 8356053) Virology. 1973 Apr;52(2):456-67. (PMID: 4705382) Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7. (PMID: 271968) Nature. 1982 Oct 7;299(5883):555-7. (PMID: 6750410) Science. 1984 May 4;224(4648):497-500. (PMID: 6200935) Nature. 1985 Jan 24-30;313(6000):277-84. (PMID: 2578615) |
|---|---|
| Substance Nomenclature: | 0 (Gene Products, gag) 0 (HIV Antigens) 0 (HIV Core Protein p24) 0 (HIV Protease Inhibitors) 0 (Oligopeptides) 0 (Viral Proteins) 0 (gag Gene Products, Human Immunodeficiency Virus) 0 (p17 protein, Human Immunodeficiency Virus Type 1) 04Y7590D77 (Isoleucine) 139694-65-8 (KNI 102) EC 3.4.23.- (HIV Protease) HG18B9YRS7 (Valine) |
| Entry Date(s): | Date Created: 19940101 Date Completed: 19940113 Latest Revision: 20200724 |
| Update Code: | 20231215 |
| PubMed Central ID: | PMC236282 |
| DOI: | 10.1128/JVI.68.1.233-239.1994 |
| PMID: | 8254733 |
| Autor: | el-Farrash MA; Department of Biodefence and Medical Virology, Kumamoto University School of Medicine, Japan., Kuroda MJ, Kitazaki T, Masuda T, Kato K, Hatanaka M, Harada S |
| Jazyk: | angličtina |
| Zdroj: | Journal of virology [J Virol] 1994 Jan; Vol. 68 (1), pp. 233-9. |
| DOI: | 10.1128/JVI.68.1.233-239.1994 |
| Abstrakt: | A synthetic peptide, RPI 312, that specifically inhibits the protease of the human immunodeficiency virus type 1 (HIV-1) showed a potent inhibition on virus production, maturation, and infectivity. Treatment with this agent prevented the cleavage of Gag protein at the site between p17 and p24 in HIV-1 chronically infected MOLT-4 cells as well as in the released virus. Passage of HIV-1 in the presence of gradually increasing concentrations of this protease inhibitor resulted in emergence of a variant that could evade the drug effects. In the resistant variant the maturation of Gag proteins appeared normal, but its infectivity was reduced compared with that of the parent virus. The nucleotides coding the amino acids at and around the cleavage site between Gag proteins p17 and p24 were not changed. One point mutation (A-->G) at site 2082 of the pol gene that resulted in one amino acid change at site 84 of the protease from isoleucine to valine (I-84-->V) could be detected in the resistant variant. An HIV-1 infectious DNA clone with the I-84-->V mutation also showed reduced sensitivity to this protease inhibitor. The findings that the resistant variant had lower infectivity and was still affected by higher doses of the drug support the speculation that resistance to protease inhibitors may not be as problematic as other drug resistance. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|