This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mo, H.
Right arrow Articles by Molla, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mo, H.
Right arrow Articles by Molla, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2007, p. 732-735, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00690-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Identification and Structural Characterization of I84C and I84A Mutations That Are Associated with High-Level Resistance to Human Immunodeficiency Virus Protease Inhibitors and Impair Viral Replication{triangledown}

Hongmei Mo,2 Neil Parkin,3 Kent D. Stewart,1 Liangjun Lu,1 Tatyana Dekhtyar,1 Dale J. Kempf,1 and Akhteruzzaman Molla1*

Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois,1 Gilead Sciences, Foster City, California,2 Monogram Biosciences, Inc., South San Francisco, California3

Received 5 June 2006/ Returned for modification 20 July 2006/ Accepted 3 November 2006

Two novel human immunodeficiency virus protease mutations, I84C and I84A, were identified in patient isolates. The mutants with I84C displayed high-level resistance (median, at least 56-fold) to nelfinavir and saquinavir, but the majority remained susceptible to lopinavir. In contrast, isolates with the I84A mutation exhibited ≥33-fold median increased levels of resistance to nelfinavir, indinavir, amprenavir, ritonavir, lopinavir, saquinavir, and atazanavir. Isolates with the I84A or I84C mutation tended to be more resistant than the isolates with the I84V mutation. Modeling of the structure of the mutant proteases indicated that the I84V, I84C, and I84A mutations all create unoccupied volume in the active site, with I84A introducing the greatest change in the accessible surface area from that of the wild-type structure.

* Corresponding author. Mailing address: Department R4CQ, Building AP52N, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064-6217. Phone: (847) 938-1094. Fax: (847) 938-2756. E-mail: Akhter.m.molla{at}abbott.com.

{triangledown} Published ahead of print on 13 November 2006.

Antimicrobial Agents and Chemotherapy, February 2007, p. 732-735, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00690-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lambert-Niclot, S., Flandre, P., Canestri, A., Peytavin, G., Blanc, C., Agher, R., Soulie, C., Wirden, M., Katlama, C., Calvez, V., Marcelin, A.-G. (2008). Factors Associated with the Selection of Mutations Conferring Resistance to Protease Inhibitors (PIs) in PI-Experienced Patients Displaying Treatment Failure on Darunavir. Antimicrob. Agents Chemother. 52: 491-496 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»