Scientists have found a molecule that interferes with the formation of infectious Human immunodeficiency virus (HIV) particles. The findings, reported in two papers in the August issue of Nature Structural & Molecular Biology could lead to the development of a new class of HIV drugs that slow or prevent the progression of HIV in individuals.
More than 40 million people globally are currently infected with HIV, the causative agent of AIDS, and approximately 5 million people become infected each year. The current treatment for HIV infection involves a combination of drugs that interfere with the activity of proteins crucial for the production of new HIV particles and those that block the entry of the virus into the cell. While the combination therapy has been highly successful, the emergence of HIV strains resistant to more than one of these drugs has made the identification of alternative targets a high priority.
HIV-1 is released from the infected cell as an immature, noninfectious particle with a protein shell composed of Gag proteins. Formation of the infectious particle requires the cleavage of Gag into smaller proteins. One of these smaller proteins, called capsid, must interact with other capsid proteins to form the mature, infectious virus. Now, Hans-Georg Kräusslich and colleagues identify a 12 amino acid peptide that binds to capsid and prevents its interactions with other capsid proteins.
In an accompanying paper, Felix Rey and colleagues show in three-dimensional detail how the peptide interferes with capsid-capsid interactions.
These studies identify the first inhibitor directed against the transformation of immature HIV-1 into infectious particles, which can be developed for antiviral treatment. Furthermore, these studies identify the immature virus particle as a new target for drug design.
Hans-Georg Kräusslich (Hygiene-Institut, Heidelberg, Germany)
Felix Rey (CNRS, Gif-sur-Yvette, France)
Additional contact for comment on papers:
Volker M. Vogt (Cornell University, Ithaca, NY, USA)
Abstracts of the papers are available online: Paper 1 and Paper 2.
(C) Nature Structural & Molecular Biology press release.
Message posted by: Trevor M. D'Souza