Wednesday, 31 December 2014

Inhibitor And Host Proteins Lock-In HIV

The mechanism of how HIV drug PF74 works on the virus has been visualised for the first time by a research team in Texas. PF74, known to inhibit HIV-1, binds a structural pocket on the surface of the viral container, known as the capsid, locking its genetic material inside. Proteins native to the host cells, called CPSF6 and NUP153, also bind to the same pocket, the same study revealed.

[caption id="attachment_116" align="alignleft" width="300"]Scanning electron micrograph, if you're interested. Very nice indeed. HIV (green) attacking a lymphocyte blood cell. Photo credit: C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus, CDC. CC2.0[/caption]

HIV-1 is the most common strain of the HIV retrovirus, which affects the immune system of those infected, often leading to a condition called Acquired Immunodeficiency Syndrome (AIDS). The capsid forms the protective outer layer of the HIV retrovirus and interacts with the surface of the host cell during infection.

Once inside the cell, the capsid releases the viral genetic material (RNA in the case of HIV) so the virus can replicate using the cell’s own machinery. It is unknown precisely when the HIV capsid disassembles after gaining entry to the cell.

Dr Dmitri Ivanov, author on the paper at The University of Texas Health Science Center, said that this study offers clues as to the nature of HIV-1 disassembly. The team used X-ray crystallography, a technique to show molecules in a 3D arrangement, to visualise the interactions between proteins and CA pockets of the HIV capsid – which Dr Ivanov called “illuminating”.

Dr Ivanov added “We now know how PF74 and CPSF6 interact with the adjacent building blocks of the HIV-1 capsid, thus stabilizing the entire capsid structure. It tells us that these molecules bind to the capsid before disassembly, blocking viral replication.”

It is hoped that this new understanding of the HIV capsid can be targeted for future HIV therapies.

No comments:

Post a Comment