Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Full-length HIV-1 gag determines protease inhibitor susceptibility within in-vitro assays
AIDS, Volume 24, No. 11, Year 2010
Notification
URL copied to clipboard!
Description
Objective: There is evidence that gag contributes to protease inhibitor susceptibility in treatment-experienced patients. Moreover, protease inhibitor resistance-associated mutations can arise in gag in the absence of protease mutations in vitro. We wished to assess the contribution of full-length Gag to protease inhibitor susceptibility in viruses unexposed to protease inhibitors, in particular from the most common HIV-1 subtypes, namely subtype A and C. Design: We compared the drug resistance profiles of subtype A and C cognate gag-protease (from viruses not previously exposed to protease inhibitor) to protease combined with a generic subtype B gag as in routine phenotypic testing. Methods: We amplified gag-protease sequences from plasma-derived virus or molecular clones, and used a single cycle transfection-based drug resistance assay to compare the fold changes in the concentration of drug required to inhibit 50% of viral replication of these viruses to a generic subtype B. We made a series of chimeras to explore phenotypes further. Results: In some cases, use of protease sequences without the cognate gag overestimated susceptibility to protease inhibitors, in particular to lopinavir. We provide evidence that gag sequences from wild-type viruses can contribute as much as 14-fold reduction in susceptibility to lopinavir, and that cognate protease can balance this by partially restoring susceptibility. Conclusion: Our findings demonstrate the importance of considering protease inhibitor susceptibility in the context of full-length gag, particularly with respect to the range of HIV-1 subtypes circulating worldwide. © 2010 Lippincott Williams & Wilkins.
Authors & Co-Authors
Gupta, Ravindra K.
United Kingdom, London
Medical Research Council
McCormick, Adele L.
United Kingdom, London
Medical Research Council
Towers, Greg J.
United Kingdom, London
Medical Research Council
Morris, Lynn G.
United Kingdom, London
Medical Research Council
United Kingdom, London
Public Health England
Parry, Chris M.
United Kingdom, London
Medical Research Council
United Kingdom, London
Public Health England
Statistics
Citations: 58
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1097/QAD.0b013e3283398216
ISSN:
14735571
Research Areas
Infectious Diseases