Braking the Virus
The traditional way to attenuate a virus is through trial and error — a process of selecting harmless versions. But now, attenuation can be engineered. The idea is to rewrite some of the virus’s genes using “slow” combinations of codons. The virus makes the same proteins it did before, but it makes them so slowly that an infection cannot get going.
In a recent series of experiments investigating whether such engineering actually works in practice, polioviruses with rewritten genes were 1,000 times less efficient than the viruses found in the wild. This successfully rendered the virus harmless while still letting the immune system get a good look at it: mice that had been exposed to the engineered version were immune to wild poliovirus, whereas mice that had not been were not.
Braking the Virus – Olivia Judson – Evolution – Opinion – New York Times Blog.
An interesting concept. Attenuation of bacterial strains to prevent disease and make vaccines have been well known for many years and gave us disease fighting tools such as BCG. The current tuberculosis vaccine is a live vaccine derived from Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy.
BCG vaccine, which is derived from an attenuated strain of the mycobacterium bovis when given to people helped mount an immune response that would help in case the real thing – Mycobacterium tuberculosis came along.
Tuberculosis is an infectious disease of enormous global importance. It is estimated that about one third of the human population is latently infected with Mycobacterium tuberculosis with 1.6 million people dying annually from the disease. The currently employed tuberculosis vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG) was originally derived from a virulent strain of M. bovis back to 1921, by repeated passages on potato slices soaked in glycerol-ox byle. The primary attenuation is attributed to loss of RD1 locus, which affects a protein secretion pathway. Subsequent propagation of BCG in several laboratories around the world resulted in further in vitro evolution, which is still ongoing.
It would be interesting to see where the new technique of attenuation, applied to viruses, would take us. Hopefully it would help us mount an adequate response – no pun intended – to the present day scourge, HIV. The HIV virus replicates rapidly and changes a lot in the interim such that the body is unable to adequately mount a response [1]. The immune system is also unable to get a “good look” at the virus as the envelope is hidden by various proteins. Virus attenuation may be able to slow down HIV replication enough to help the body form truly neutralizing antibodies.
References
1) An HIV vaccine–challenges and prospects.
