HIV in arms race with human immune system, study reveals

HIV (human immunodeficiency virus) is evolving rapidly to get round the weaponry of the human immune system, according to new research by an international team of scientists. The findings highlight the difficulty of developing an effective vaccine against the fast-evolving virus. The study, which was partly funded by a Marie Curie grant from the EU, was published online by the journal Nature.

At the heart of the human immune system is a set of highly specialised proteins called human leucocyte antigens (HLA). These proteins present fragments of the HIV virus to HIV-specific T-cells; in this way, they help the immune system to recognise and destroy cells that are infected with the virus.

We inherit the genes that code for the HLA proteins from our parents, and so different people produce slightly different HLA proteins. These differences help to explain why some HIV positive people can survive without anti-HIV therapy for many years, while others develop AIDS (acquired immune deficiency syndrome) in a matter of months. Furthermore, certain HLA variants are more common in some parts of the world than others. However, all too often the HIV virus mutates in ways that allow it to escape from the most effective HLA proteins.

In this latest study, the scientists set out to investigate how HIV is adapting to human immune responses. To do this, they analysed the genetic sequences of HLA genes and the HIV virus in over 2,800 HIV patients from 5 different continents.

The scientists found that the mutations that allow HIV to escape from an immune response linked to a specific HLA gene were most common in populations where that HLA gene was also common.

For example, a gene called HLA-B*51 is extremely effective at controlling HIV. However, in most people with this HLA gene, the virus rapidly develops a mutation to evade the proteins produced by the gene. In Japan, HLA-B*51 is quite common, and the researchers found HIV escape-mutation in 66% of the people who did not have the HLA-B*51 gene. In contrast, in the UK and Africa, where the HLA-B*51 gene is rarer, this figure drops to between 15% and 25%.

"Where a favourable HLA gene is present at high levels in a given population, we see high levels of the mutations that enable HIV to resist this particular gene effect," explained Professor Rodney Phillips of Oxford University in the UK. "The virus is outrunning human variation, you might say."

"We saw similar effects in every mutation that we looked at," added his colleague Professor Philip Goulder. "This shows that HIV is extremely adept at adapting to the immune responses in human populations that are most effective at containing the virus."

The findings have implications for the design of HIV vaccines, as vaccines would typically seek to boost the most effective natural immune responses.

"The implication is that once we have found an effective vaccine, it would need to be changed on a frequent basis to catch up with the evolving virus, much like we do today with the flu vaccine," commented Professor Goulder.

Meanwhile, Professor Christian Brander of Spain's Institut de Recerca de la Sida IrsiCaixa emphasises that: "this new study makes it clear that vaccine design needs to go hand in hand with human genetic studies that will help to identify differences, but also common traits, in the vaccine population."

However, Professor Goulder has an optimistic view of the findings. "The temptation is to see this as bad news, that these results mean the virus is winning the battle," he said. "That's not necessarily the case. It could equally be that as the virus changes, different immune responses come into play and are actually more effective."

Currently, over 33 million people are living with HIV around the world, and over 2.5 million are infected every year. The disease has already killed at least 25 million.

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