Outsmarting HIV with X-Ray Crystallography

Dr, Alian Akram, Lorry I. Lokey Center for Life Science & Engineering, Technion.

Outsmarting HIV


It sound like modern warfare, and indeed, even when aiming to outsmart a killer virus on a scale of about 100 nanometers, the latest technology makes all the difference. One of the deep passions behind Dr. Alian Akram’s pioneering crystallographic work in the Technion is a desire to advance treatments for HIV, the causative agent of AIDS.


Scientists in Akram’s lab investigate the general principles of how aggressive virus lock into the genetic resources of a patient – and how to prevent them from doing this. “It is a MUST to learn about the critical interactions and the mechanisms of resistance,” says Akram. The team is taking a sharp look at pathogen-host interaction and how the HIV virus literally hijacks the machinery of the host cell in order to replicate itself, and how it escapes the immune system. “We are hoping to determine the structures of key interacting molecules and develop new intervening strategies and drugs that prevent their interaction. We also want to understand the mechanism of emergent resistance in the proteins of this virus.”


Current drugs for HIV bind viral proteins – and yet it continues to mutate and regenerate. Akram’s team is working on a protein discovered in 2004 – intrinsic immunity APOBEC3G. This protein attacks the genome of HIV and causes hypermutation that leads to an abortive replication cycle for HIV. However, HIV expresses a protein that destroys APOBEC, so the Akram’s group wants to understand this process better so that it can be blocked.
Crystal structure of Pseudouridine synthase in complex with RNA solved by  Akram Alian. The structure reveals base-pair rearrangement as the key mechanism to rRNA substrate selectivity  (http://rnajournal.cshlp.org/content/16/6.cover-expansion)”