Email updates

Keep up to date with the latest news and content from Retrovirology and BioMed Central.

Open Access Highly Accessed Research

Natural variation of HIV-1 group M integrase: Implications for a new class of antiretroviral inhibitors

Soo-Yon Rhee1, Tommy F Liu1, Mark Kiuchi1, Rafael Zioni1, Robert J Gifford1, Susan P Holmes2 and Robert W Shafer1*

Author Affiliations

1 Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, USA

2 Department of Statistics, Stanford University, Stanford, CA, USA

For all author emails, please log on.

Retrovirology 2008, 5:74  doi:10.1186/1742-4690-5-74

Published: 7 August 2008

Abstract

HIV-1 integrase is the third enzymatic target of antiretroviral (ARV) therapy. However, few data have been published on the distribution of naturally occurring amino acid variation in this enzyme. We therefore characterized the distribution of integrase variants among more than 1,800 published group M HIV-1 isolates from more than 1,500 integrase inhibitor (INI)-naïve individuals. Polymorphism rates equal or above 0.5% were found for 34% of the central core domain positions, 42% of the C-terminal domain positions, and 50% of the N-terminal domain positions. Among 727 ARV-naïve individuals in whom the complete pol gene was sequenced, integrase displayed significantly decreased inter- and intra-subtype diversity and a lower Shannon's entropy than protease or RT. All primary INI-resistance mutations with the exception of E157Q – which was present in 1.1% of sequences – were nonpolymorphic. Several accessory INI-resistance mutations including L74M, T97A, V151I, G163R, and S230N were also polymorphic with polymorphism rates ranging between 0.5% to 2.0%.