Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2017

Erindi/veggspjald / Talk/poster E25

The maedi-visna virus intasome

Höfundar / Authors: Stefán Ragnar Jónsson (1), Valgerður Andrésdóttir (1), Allison Ballandras-Colas (2), Peter Cherepanov (2)

Starfsvettvangur / Affiliations: 1. Institute for Experimental Pathology, University of Iceland, 2. The Francis Crick Institute, London

Kynnir / Presenter: Stefán Ragnar Jónsson

Maedi-visna virus (MVV) is a member of the lentivirus subfamily of retroviruses, causing encephalitis (visna), pneumonia (maedi), mastitis and arthritis in sheep. Other family members include the simian and human immunodeficiency viruses (SIV and HIV). All retroviruses reverse transcribe their RNA into a linear double-stranded viral DNA which is then integrated into the host cell chromosomes with the aid of the viral enzyme integrase. Integration is thus an important antiviral target in the fight against HIV/AIDS. However, HIV integrase is a notoriously difficult protein to work with, which has made it necessary to introduce hyperactive and solubilizing mutations, which, by their nature, dramatically change protein properties. In this study, the structure of the MVV intasome (integrase complex with viral DNA) was determined using cryo-electron microscopy. The maedi-visna virus intasome contained sixteen integrase subunits with a tetramer-of tetramer architecture, interacting with the two viral DNA ends. This is a more complex intasome structure than that of other retroviruses, where the PFV (foamy virus) intasome contains a tetramer and alpha- and betaretroviruses have an intasome composed of two integrase tetramers. The structure of the maedi-visna virus intasome can explain much of previous data on HIV-1 structure and provide a lentiviral platform for design of HIV-1 integrase inhibitors.