The HIV family of lentiviruses carry 'accessory proteins' that
recruit a host cell's own machinery to break down one of its
antiviral defence proteins.
Vpx, accessory proteins found in HIV-2 and SIV (close relatives
of HIV-1, the main cause of the global AIDS pandemic) target a host
antiviral defence protein called SAMHD1. To do this, they
manipulate a host receptor protein called DCAF1.
By uncovering the three-dimensional structure of Vpx bound to
SAMHD1 and DCAF1, Francis Crick Institute researchers currently
based at Mill Hill Laboratories have revealed how the Vpx from
different viruses use different strategies to recruit SAMHD1.
For their study, the team used X-ray crystallography to
determine the structure of Vpx from an SIV virus isolated from
mandrill monkeys, as well as DCAF1 and SAMHD1. The scientists
compared their result with a structure they had previously
determined of a complex containing a Vpx from another lentivirus to
reveal how all Vpx proteins interact with DCAF1 in a common manner
but differ in the way they recruit SAMHD1.
Dr Ian Taylor of the Crick said: "It is now clear that
lentiviruses (the virus family that includes HIV) carry accessory
proteins that have the sole purpose of targeting cellular factors
that inhibit retroviral infection.
Commenting on the implications of the work for treating
HIV/AIDS, "The 3D structure of this protein complex reveals in
molecular detail how these factors have adapted to be able to
this."
Dr Taylor added: "Disrupting the interaction of viral accessory
proteins such as Vpx with the host cell factor DCAF1 would be a
completely new way of disrupting HIV-1 replication by boosting the
cell's own natural defence to the virus."
The paper,Molecular Determinants for Recognition of Divergent SAMHD1 Proteins
by the Lentiviral Accessory Protein Vpx, is published
in Cell Host and Microbe.