Taming the "Flu" virus

Author:  Metcalfe David

Date:  February 2008

In the age of cancer, diabetes, and heart disease, it is a bold scientist who stakes his research career on an everyday' illness like the flu. Nigel Dimmock, Emeritus Professor of Virology at the University of Warwick, is one such scientist. A virologist by training, Professor Dimmock has spent over forty years locked in combat with the influenza virus. Now, as the UN warns of a bird flu' pandemic with the potential to kill millions, Dimmock's team is poised to deliver their final strike against influenza. According to their paper published in the journal Vaccine, they have created a protecting virus' which tackles influenza within the body. Having successfully tested their virus on ferrets, the team is hoping to commence human clinical trials in the near future.

The influenza virus is a small infectious agent which can reproduce inside bird and mammalian cells. Under a powerful microscope, each virus particle can be observed as genetic material surrounded by a protective protein coat called a capsid'.

Most vaccinations work by injecting a small amount of capsid into the body. The immune system recognises the foreign capsid and creates antibodies, which destroy the foreign material. However, a small number of specific antibodies persist in the circulation even after the vaccine has eliminated their target. When the body becomes infected by a live virus, it is recognised by the remaining antibodies which set up an intense immune response and quickly end the infection. Although this vaccination strategy works for illnesses such as polio and smallpox, influenza makes many different capsids and so can evade antibody detection.

Now, scientists may have finally outsmarted influenza. Dimmock's vaccine is itself a type of influenza virus, except his strain has been genetically engineered so that it is harmless. The genes that the virus needs for replication have been removed and, as a result, the virus cannot spread through the body or infect other people.

Although unable to harm humans, Dimmock's creation can devastate other influenza infections. It does this by infecting potential host cells and lying in wait for a harmful virus to come along. When a normal influenza strain infects one of these protected' cells, it produces proteins which are required for the protecting virus to replicate. This exploits a technology known as defective interference RNA in which a tame viral strain is used to interfere with the actions of its harmful relative. In their paper the authors write "defective RNA can only replicate when the protein or proteins it is unable to synthesize are supplied . by infectious virus." As the protecting viral genome is smaller, it is produced faster than the normal strain which is unable to compete efficiently enough for resources. "Its small size", write the authors, "may confer a replication advantage over the full-length RNA, and is responsible for the interference phenomenon."

Once the harmful infection is slowed, the body has time to develop antibodies specific for the type of capsid used by the infecting strain. As a result, the protecting virus converts every new influenza infection into a vaccine against itself and so has little to fear from changes to the viral capsid.

"Because [the] interfering vaccine acts intracellularly and at a molecular level, it should be effective against all influenza A viruses regardless of subtype," wrote the authors in their paper. Furthermore, "This raises the possibility for this technology to be used against other highly mutating viruses such as HIV.

Written by David Metcalfe

Reviewed by Nira Datta, Pooja Ghatalia

Published by Pooja Ghatalia.