A single polymorphism in HIV-1 subtype C SP1 is sufficient to confer natural resistance to the maturation inhibitor bevirimat

Antimicrobial Agents and Chemotherapy

Volumn 55, Issue 7, 2011, Pages 3324-3329

  Lu, Wuxun ^a   Salzwedel, Karl ^b,d   Wang, Dan ^a   Chakravarty, Suvobrata ^a   Freed, Eric O ^c   Wild, Carl T ^b,e   Li, Feng ^a  

^a SOUTH DAKOTA STATE UNIVERSITY   (United States)

^b Panacos Pharmaceuticals   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

^d NATIONAL INSTITUTES OF HEALTH   (United States)

^e DFH Pharma   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BEVIRIMAT; GAG PROTEIN; GAG SP1 PROTEIN; MPC 4326; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; AMINO TERMINAL SEQUENCE; ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CHIMERA; CONTROLLED STUDY; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN PROCESSING; SINGLE NUCLEOTIDE POLYMORPHISM; VIRION; VIRUS CAPSID; WESTERN BLOTTING;

ANIMALS; ANTI-HIV AGENTS; BLOTTING, WESTERN; CERCOPITHECUS AETHIOPS; COS CELLS; DRUG RESISTANCE, VIRAL; ELECTROPHORESIS, POLYACRYLAMIDE GEL; GAG GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; POLYMORPHISM, GENETIC; TRITERPENES;

EID: 79959241949     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01435-10     Document Type: Article

References (21)

1. Accola, M. A., S. Hoglund, and H. G. Gottlinger. 1998. A putative alpha-helical structure which overlaps the capsid-p2 boundary in the human immunodeficiency virus type 1 Gag precursor is crucial for viral particle assembly. J. Virol. 72:2072-2078.
2. Adamson, C. S., et al. 2006. In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor BVM (bevirimat). J. Virol. 80: 10957-10971.
3. Adamson, C. S., M. Sakalian, K. Salzwedel, and E. O. Freed. 2010. Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV-1 maturation inhibitor bevirimat. Retrovirology 7:36.
4. Adamson, C. S., K. Waki, S. D. Ablan, K. Salzwedel, and E. O. Freed. 2009. Impact of human immunodeficiency virus type 1 resistance to protease inhibitors on evolution of resistance to the maturation inhibitor bevirimat (BVM). J. Virol. 83:4884-4894.
5. Grisson, R. D., et al. 2004. Infectious molecular clone of a recently transmitted pediatric human immunodeficiency virus clade C isolate from Africa: evidence of intraclade recombination. J. Virol. 78:14066-14069. (Pubitemid 39612806)
6. Kantor, R., et al. 2005. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration. PLoS Med. 2:e112.
7. Li, F., et al. 2003. BVM: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc. Natl. Acad. Sci. U. S. A. 100:13555-13560.
8. Li, F., et al. 2006. Determinants of activity of the HIV-1 maturation inhibitor BVM. Virology 356:217-224. (Pubitemid 44750029)
9. Liang, C., et al. 2002. Characterization of a putative alpha-helix across the capsid-SP1 boundary that is critical for the multimerization of human immunodeficiency virus type 1 Gag. J. Virol. 76:11729-11737. (Pubitemid 35231328)
10. Margot, N. A., C. S. Gibbs, and M. D. Miller. 2010. Phenotypic susceptibility to bevirimat in isolates from HIV-1-infected patients without prior exposure to bevirimat. Antimicrob. Agents Chemother. 54:2345-2353.
11. Martin, D. E., R. Blum, J. Doto, H. Galbraith, and C. Ballow. 2007. Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers. Clin. Pharmacokinet. 46:589-598.
12. Martin, D. E., et al. 2007. Safety and pharmacokinetics of bevirimat (BVM), a novel inhibitor of human immunodeficiency virus maturation, in healthy volunteers. Antimicrob. Agents Chemother. 51:3063-3066.
13. Martin, D. E., K. Salzwedel, and G. P. Allaway. 2008. Bevirimat: a novel maturation inhibitor for the treatment of HIV-1 infection. Antivir. Chem. Chemother. 19:107-113.
14. McCallister, S., et al. 2008. HIV-1 Gag polymorphisms determine treatment response to bevirimat (BVM). Antivir. Ther. 2008:A10.
15. Ndung'u, T., B. Renjifo, and M. Essex. 2001. Construction and analysis of an infectious human immunodeficiency virus type 1 subtype C molecular clone. J. Virol. 75:4964-4972.
16. Seclen, E., et al. 2010. High prevalence of natural polymorphisms in Gag (CA-SP1) associated with reduced response to bevirimat, an HIV-1 maturation inhibitor. AIDS 24:467-469.
17. Smith, P. F., et al. 2007. Phase I and II study of the safety, virologic effect, and pharmacokinetics/pharmacodynamics of single-dose 3-o-(3′,3′-dimethylsuccinyl) betulinic acid (bevirimat) against human immunodeficiency virus infection. Antimicrob. Agents Chemother. 51:3574-3581.
18. Van Baelen, K., et al. 2009. Susceptibility of human immunodeficiency virus type 1 to the maturation inhibitor bevirimat is modulated by baseline polymorphisms in Gag spacer peptide 1. Antimicrob. Agents Chemother. 53:2185-2188.
19. Velazquez-Campoy, A., et al. 2003. Protease inhibition in African subtypes of HIV-1. AIDS Rev. 5:165-171. (Pubitemid 37336633)
20. Zhou, J., C. H. Chen, and C. Aiken. 2004. 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 1:15.
21. Zhou, J., et al. 2004. Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation. J. Virol. 78:922-929. (Pubitemid 38067613)