[MOAA2LB] Ability to detect and to manipulate HIV-1 evolution via recombination – a new tool to suppress the generation of multiple drug resistant and immune escape HIV-1

4th International AIDS Society Conference on HIV Pathogenesis and Treatment

Sydney, Australia - July 22 - 25, 2007

ABILITY TO DETECT AND TO MANIPULATE HIV-1 EVOLUTION VIA RECOMBINATION – A NEW TOOL TO SUPPRESS THE GENERATION OF MULTIPLE DRUG RESISTANT AND IMMUNE ESCAPE HIV-1

IAS Conf HIV Pathog Treat 2007 Jul 22-25;4th: Abstract No. MOAA2LB

Smyth R.¹, Schlub T.², Tachedjian G.¹, Davenport M.², Mak J.³
¹The Burnet Institute, Melbourne, Australia, ²University of NSW, Sydney, Australia, ³The Burnet Institute, Port Melbourne, Australia

OBJECTIVES: Retroviral recombination is known to play an important role in the evolution of HIV-1 by diversifying the viral quasi-species. It is widely believed to accelerate escape from immune pressure and antiretroviral therapy, which can lead to treatment failure. Manipulation of recombination may be an important strategy through which we can control the emergence of multiple drug resistant (MDR) HIV-1, and enhance the efficacy of antiretroviral therapy.

METHODS: We have developed a novel HIV-1 marker system by making a small number of codon modifications in gag and pol, to mimic the quasi-species in an infected individual where viral genome sequences and structure are highly related.

RESULTS: Using this system, we have compared recombination rates under different treatments: The rate of recombination is significantly reduced in gag by deletion of the dimerization initiation site (DIS) (p<0.05). The estimated rate of recombination was also reduced ~26% in neomycin treated cells, although this was not statistically significant. This marker system can be used to identify recombination ‘hotspots’ in the genes. Our data suggested that the average rate of recombination is higher in macrophages compared to T cells. More importantly, we are able to manipulate the recombination process by targeting the viral RNA structures, such as deletion of the dimerization initiation site (DIS).

CONCLUSIONS: Here we present the first direct proof of concept evidence that retroviral recombination can be regulated. Our results support the development of novel compounds to regulate HIV-1 evolution, to ultimately suppress the emergence of MDR HIV-1 and immune escape HIV-1.

Download PDF of this abstract.

2007-07-22
MOAA2LB
HIV Diversity, Tropism and Compartmentalization

Copyright © 2007 - International AIDS Society (IAS). All information and content relating to the abstracts from the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2007. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2007. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.