The biological arms race between the AIDS virus and the immune system

A research group from the University of Oxford has revealed that the HIV virus is undergoing rapid evolution, side by side with the immune system of human populations.

We've known for a long time that viruses are a bunch of trouble. Vaccines are our best way to deal with viral diseases, but viruses can bypass vaccines through rapid evolution. The flu virus, for example, undergoes an evolution every year, which allows it to re-attack the population that acquired a vaccine against the previous version last year. The HIV virus is also able to accumulate mutations very quickly, which allow it to evade the human immune system. Will it one day be possible to find an effective vaccine against HIV that will withstand the rapid evolution it undergoes?

"Even in the short time that HIV has existed in the human population, it manages to effectively evade the immune system's best attempts to control the virus. We are witnessing a high-speed evolution, occurring in a time interval of a few decades." says Professor Philip Golder, the lead researcher in the research group that examined the evolution of the virus in the human population.

The HIV virus has already killed 25 million people, and the current estimate is that another 33 million have already been infected. But HIV does not kill all humans at the same rate. On average, an adult with HIV will develop the immune deficiency syndrome within ten years, if they do not use anti-HIV drugs. From the moment the immune system fails, the patient's days are numbered. But in some carriers, the immune system will fail in just 12 months, while in others it will fail only after twenty years or more.

In the immune system there are genes that code for a very important group of molecules called HLA - Human leucocyte antigens. The HLA molecules determine how the body will be able to deal with many infectious diseases, including HIV, and allow the immune system to identify and kill cells infected with the virus. Humans differ from each other in the specific HLA genes they carry, and small differences between the genes can allow the body to delay the spread of the HIV virus in the body, and extend the time until the body succumbs to the virus.

A research group in Oxford decided to try and test whether the HIV virus changes according to the human immune systems it encounters. They examined genetic sequences of the virus from different countries around the world, including England, South Africa, Botswana, Australia, Canada and Japan, in an attempt to check whether it is possible to link the genetic sequences of the virus with the various HLA genes present in different populations.

The group held collaborations between the University of Oxford, the Ragon Institute at Massachusetts General Hospital, Kumamoto University in Jaffa, the Royal Perth Hospital and Murdoch University in Australia and others. As part of the joint work, the different groups analyzed the genetic sequences of the HIV virus and the HLA genes in more than 2,800 people.

It turned out that the mutations that allow the virus to evade the immune responses activated by a certain HLA gene, were found at a higher frequency in human populations where there was a high frequency of that HLA gene. This is good evidence of the ability of the virus to adapt to the human immune system at the population level.
"When a successful HLA gene is present at a high level in a certain population, we see high levels of the mutations that allow HIV to resist the effect of that particular gene," says Professor Rodney Phillips, author of the paper recently published in Nature and one of the directors of the James Martin Institute for Emerging Diseases at the University of Oxford. "You can say that the virus is bypassing human diversity."

"The temptation is to see this as bad news, that these results indicate that the virus is winning the battle," says Professor Gorder. "This is not necessarily the case. It is equally possible that when the virus changes, different immune responses come into play and are actually more effective."

Despite Golder's optimism, it seems that the importance of the research results lies in the conclusions for the future of HIV treatment. In the future, vaccines against HIV will try to increase the level of protection of the body's immune system, to a level where it can fight the virus on equal terms.

"The meaning is that once we find an effective vaccine, we will have to change it on a regular basis, to keep up with the evolving virus, similar to the way we currently do with the flu virus," explains Professor Golder.

"...we are used to thinking of evolution as occurring over thousands, tens of thousands and even millions of years," says Professor Golder. "But we see changes in HIV, and in the immune response to the virus, in a short time of a few decades."

For information on the Oxford University website

For the Scientific American series that was published in parts on the Hidan website:

• Part I - AIDS: the great challenges
• Part B - Can AIDS be cured?
• The third part will be published tomorrow