The research is helping scientists
understand how HIV 'outsmarts' our
immune system.
Image: iStockphoto 

Researchers at the University of Melbourne have gained new insight into the immune system’s response to HIV and are one step closer to understanding how to develop preventative and therapeutic vaccines.

The study, by PhD student and lead author Ms Liyen Loh, from the Department of Immunology and Microbiology, focused on the interplay between the virus and the immune system, and how this affects the replication of the HIV virus in the body.

Supervised by Professor Stephen Kent, who is internationally recognised for his work in the HIV immunology field and for developing and testing HIV vaccines, the study also looked at why some individuals have better clinical outcomes after treatment than others.

“Knowing what factors are important for controlling HIV replication can help guide vaccine studies. Our research has 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,” says Ms Loh.

Major players in the body’s immune system are killer T cells, as they have the ability to identify and attack virus-infected or cancerous cells.

“HIV can ‘out-smart’ these killer T cells, however, by mutating to a slightly different form that can no longer be recognised by the killer T cells,” says Ms Loh.

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 the generation of fewer copies.

“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,” she says.

“This helps explain why some individuals have better clinical outcomes than others.”

Researchers measured the length of time it took for the 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,” says Ms Loh.

“Once HIV gets into an individual, it mutates to ‘adapt’ to the immune response of that person.

“Because all our immune systems are subtly different, 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.”

It is now possible to measure how fast this reversion occurs, and how this can have an impact on the overall level of virus.

“If the slow-growing form persists for a long time, this can reduce the ‘fitness’ of the virus and its ability to spread within the new host,” she says.

This may have clinical significance, as individuals with a population of less-fit virus may have a more functional immune system. The study, in collaboration with researchers at the University of New South Wales, was published in the Public Library of Science journal, Pathogens.