One in 10 children appear to have a ‘primate like’ defence against Aids

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childrenwebA new study has revealed for the first time that a small group of HIV-infected South African children have evolved a unique, ‘primate like’ immune system that protects them from developing Aids, says a Science Alert report.

Normally, without treatment, more than half of all children with HIV worldwide will die before they’re two years old, but previous research has shown that up to 10% of infected kids will never get symptoms from the infection, making them “paediatric non-progressors” – and now we finally know why.

The report says the new study shows that, similar to non-human primates, the immune systems of these kids don’t freak out when they come into contact with HIV, and this keeps the infection from getting out of control.

It’s hoped that we can now learn from these children, and use them as a model to develop better HIV treatments in the future, the report says.

When someone is infected with HIV, the virus usually hijacks the body’s immune system, and gradually wipes out its white blood cell population, leaving the patient vulnerable to all other infections – a state called acquired human immunodeficiency syndrome, or Aids.

When a patient has Aids, even a common cold can be fatal, but current antiretroviral treatments allow people to live relatively healthy lives by suppressing HIV before it progresses to this stage.

A new study analysed 170 South African children under the age of five who were paediatric non-progressors – in other words, who have HIV but have never had Aids, despite not undergoing antiretroviral therapy. And the results showed that their immune systems had a totally different response to HIV.

These kids had tens of thousands of HIV particles in every millilitre of their blood – something that would usually drive a person’s immune system into crazy defensive action against the virus, and make them seriously ill. But neither was happening to these kids.

“Essentially, their immune system is ignoring the virus as far as possible,” one of the researchers, Philip Goulder, from the University of Oxford is quoted in the report as saying. “Waging war against the virus is in most cases the wrong thing to do.”

That’s because when the immune system goes into overdrive against HIV, even more white blood cells can be killed by chronic inflammation levels, leading to a speedier wipe out of the immune system. By simply not fighting back, it appears the immune system can bunker down and survive an infection.

The report says interestingly enough, this is also the strategy taken by 40 species of non-human primates, which are also able to survive an HIV infection by not allowing it to progress to Aids. “Natural selection has worked in these cases,” said Goulder, “and the mechanism is very similar to the one in these kids that don’t progress.”

And, the report says, in humans, the strategy is pretty much unique to kids. Scientists have spent decades studying the roughly 0.3% of adults who are able to handle HIV infection without it progressing – known as ‘elite controllers’ – but their immune systems do pretty much the opposite of these children. Instead of ‘keeping calm’, they mount an increasingly aggressive attack against the HIV virus – something that usually ends up making the infection worse when trialled in other patients.

The report says the team is now continuing to investigate whether the ‘do-less’ kid approach will work any better for future treatments – and whether or not these children continue to be protected against Aids even as they age.

“It is not known whether it would be clinically safe for these newly identified HIV infected paediatric non-progressors to remain off-therapy,” infectious disease specialists Ann Chahroudi and Guido Silvestri from Emory University in the US, who weren’t involved in the study, write in a commentary on the new research. But they do admit that the study might have found the “very earliest signs of co-evolution of HIV in humans”. “We may be identifying an entirely new pathway by studying kids that in the longer term could be translated to new treatments for all HIV infected people,” is quoted in the report as saying.

Abstract
Disease-free infection in HIV-infected adults is associated with human leukocyte antigen–mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy–naïve children aged >5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys—low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells—suggesting closer similarities with nonpathogenetic mechanisms evolved over thousands of years in natural SIV hosts than those operating in HIV-infected adults.

Authors
Maximilian Muenchhoff, Emily Adland, Owen Karimanzira, Carol Crowther, Matthew Pace, Anna Csala, Ellen Leitman, Angeline Moonsamy, Callum McGregor, Jacob Hurst, Andreas Groll, Masahiko Mori, Smruti Sinmyee, Christina Thobakgale, Gareth Tudor-Williams, Andrew J. Prendergast, Henrik Kloverpris, Julia Roider, Alasdair Leslie, Delane Shingadia, Thea Brits, Samantha Daniels, John Frater, Christian B Willberg, Bruce D Walker, Thumbi Ndung’u, Pieter Jooste, Penny L Moore, Lynn Morris, Philip Goulder

Full Science Alert report
Science Translational Medicine abstract
Science Translational Medicine commentary


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