Volume 95 Issue 2 | p. 9 | Concentrates
Issue Date: January 9, 2017

How HIV inserts DNA into host genomes

Researchers provide first image of machinery used by the virus to integrate its genetic material
Department: Science & Technology
News Channels: Biological SCENE, Analytical SCENE
Keywords: structural biology, intasome, HIV

When HIV infects a host cell, the pathogen converts its RNA code to DNA and then docks the genetic material in a host’s genome. The first glimpse of the HIV machinery that performs this insertion comes courtesy of a team of researchers led by Dmitry Lyumkis at the Salk Institute for Biological Studies (Science 2017, DOI: 10.1126/science.aah5163). Called the intasome, HIV’s insertion machinery is targeted and blocked by drugs such as raltegravir and elvitegravir. To develop these drugs and to study HIV’s intasome, scientists had relied on biochemical techniques, computer modeling, prior X-ray crystallography work describing individual domains within the insertion machinery and the structures of intasomes from related viruses, such as PFV, the prototype foamy virus. Lyumkis’s team used cryo-electron microscopy to image HIV’s intasome with a resolution of 3.5 to 4.5Å. The group found that several amino acid residues in and near the machinery’s active site are positioned differently in HIV compared with PFV. The new work “provides important guidance for rationally improving clinically relevant inhibitors,” notes the team. In another study published in Science, researchers led by Peter Cherepanov at London’s Francis Crick Institute report the cryo-electron structure of an intasome from a maedi-visna lentivirus, which could provide a platform for screening HIV intasome inhibitors (DOI: 10.1126/science.aah7002).

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HIV machinery known as the intasome (two views shown here) integrates viral DNA (dark gray) into host DNA (light gray).
Credit: Science
Image of the HIV machinery that integrates viral DNA into hosts.
 
HIV machinery known as the intasome (two views shown here) integrates viral DNA (dark gray) into host DNA (light gray).
Credit: Science
 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

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