April 29, 2009
Researchers have gained new insight into how the immune system responds to HIV. The new findings are a step closer to understanding how to develop preventative and therapeutic vaccines against HIV and why some individuals have better clinical outcomes after treatment.
PhD student and lead author Liyen Loh, from the Department of Immunology and Microbiology at the University of Melbourne said the study focussed on the interplay between virus and the immune system and how this affected the number of copies of the HIV virus in the body.
"Our research revealed that maintaining a weakened strain of the virus during the early stages of HIV infection may help the body's immune system to control virus replication. Knowing what factors are important for controlling HIV replication can also help guide vaccine studies," said Ms Loh.
Killer T cells are a major player in the host immune system as they have the ability to identify and attack virus infected or cancerous cells.
However HIV can "out-smart" killer T cells by mutating to a slightly different form that can no longer be recognised by the killer T cells. These viruses are known as escape mutants.
The study discovered these changes usually come at a "fitness cost" to the virus resulting in slower replication and fewer copies of the virus.
"When HIV is transmitted to a new host, the mutations often revert to the original wild-type virus, allowing the virus to regain a fitter state, or the changes may be retained, depending on the individual's immune system. This explains why some individuals have better clinical outcomes than others," said Ms Loh.
Researchers from the University of Melbourne and the University of New South Wales measured the length of time it took for transmitted escape mutant virus to return to its fitter wild-type state in a new host.
"We have identified several 'rules' governing how HIV escapes being detected by killer T cells," said Ms Loh. "Once HIV gets into an individual, it undergoes mutation to 'adapt' to the immune response of that person.
"All of our immune systems are subtly different so what is 'well adapted' in one patient is often slightly slow growing in a new patient. Therefore, over the first few weeks or months of infection of a new patient, the virus 'reverts' from this slow growing form to a fast growing form, while at the same time adapting to the new immune response."
The study found you can measure how fast this reversion occurs, and that this has an impact on the overall level of virus. A slow-growing form of virus with reduced 'fitness' may affect the ability to spread within the new host.
This may have potential clinical significance, as individuals with a population of less-fit virus may have a more functional immune system.
The study is published in the April edition of the Public Library of Science journal Pathogens.