Researchers from the Max Planck Institute of Biochemistry have discovered the mechanism behind an important step in the life cycle of HIV. Working together with teams at Heidelberg and Yale Universities, they found that the enigmatic “spacer peptide 2,” one of the virus components, plays a key role in converting immature HIV-1 particles into infectious particles. The results of the study were published in the journal Nature.
HIV-1 particles are released from infected cells in an immature, non-infectious form. The main building material for a virus particle is about 2,000 copies of a long, rod-shaped protein called Gag. To become infectious, HIV has to undergo a maturation process. This involves the HIV-1 protease (a viral enzyme), that cuts up Gag into six smaller proteins including the capsid protein and the matrix protein. This causes a huge structural rearrangement of the virus components.
For many years, scientists have explored the structural changes of the virus capsid which encases the genome. In contrast, much less is known about the virus matrix—the outer protein shell directly beneath the lipid membrane that envelops the virus. Researchers led by John Briggs, director and structural biologist at the Max Planck Institute of Biochemistry, have now worked out how the matrix protein rearranges during maturation into the infectious particle.
They used the latest cryo-electron microscopes to image virus particles, and then used computational image analysis to derive very detailed 3D models of the viral proteins. Unexpectedly, they found that the rearrangement of the matrix is triggered by “spacer peptide 2,” which sticks to the matrix and causes it to pack together in a different way.
