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Study suggests novel genetic mechanism behind HIV immunity

10 November 2014
Appeared in BioNews 779

Scientists claim to have discovered the genetic mechanism by which two patients developed immunity to HIV infection.

The patients - both infected with HIV, one of them infected 30 years ago - have never developed symptoms of the disease. The virus cannot be detected in their blood, even though neither have received treatment.

The 'AIDS-causing virus remained in their immune cells but was inactivated because its genetic code had been altered', the scientists, from France's Institute of Health and Medical Research (INSERM), wrote in the study.

The researchers theorised the 'change [in the genetic code of the virus] appeared to be linked to increased activity of a common enzyme called APOBEC'.

The study, which was led by Professor Didier Raoult, analysed the genome of the two patients: a 57-year-old man diagnosed with HIV in 1985, and a 23-year-old man diagnosed in 2011.

HIV typically invades the immune cells of infected people, replicating in and reprogramming these cells to become viral factories.

Both men are examples of 'elite controllers', a subset of HIV-infected patients who show resistance to the disease. Only around one percent of HIV patients are thought to show no symptoms.

The exact mechanism through which elite controllers develop resistance to HIV infection is not yet clear. But, the researchers suspect amplification in APOBEC enzyme activity inhibited the replication of HIV in the immune cells of the two patients in their study.

They believe this may have stopped the proliferation of the virus and progression of the HIV infection - effectively leading the two men to experience what they call an 'apparent spontaneous cure'.

The researchers also suggest persistence of the HIV DNA in the host cell allowed integration of the viral genome into the human genome, thereby, leading to the neutralisation of the virus - a process termed 'endogenisation'.

Previous studies have reported a similar process of endogenisation in a population of koalas who have been able to integrate an AIDS-like virus into their gene, neutralising the virus and passing on this resistance to their offspring.

According to the researchers, the study 'findings suggest that without therapeutic and prophylactic strategies, after several decades of HIV/host integrations and millions of deaths, it is likely that a few individuals might have endogenised and neutralised the virus and transmitted it to their progeny'.

Therefore, resistance to and spontaneous cure from HIV likely develops through persistence of the viral genome in host cells, the scientists have suggested.

Current treatment for HIV generally involves the use of anti-retroviral medication to remove traces of the viral genome from human cells.

The researchers propose a different approach to HIV treatment, stressing that 'integration, inactivation and potential endogenisation of viral genome into the human genome' were possibly critical for developing natural immunity to HIV infection.

The study was published in the journal Clinical Microbiology and Infection.

'Elite controllers' may provide clues for HIV cure
NHS Choices |  5 November 2014
HIV infection en route to endogenization: two cases
Clinical Microbiology and Infection |  4 November 2014
Scientists see mechanism for spontaneous HIV 'cure'
Yahoo! News (AFP) |  4 November 2014
Scientists uncover the secret of the 'elite controllers' who can spontaneously 'cure' HIV - and say it could lead to new treatments
MailOnline |  4 November 2014
So-Called HIV ‘Cure’ Is Not Actually a Cure
Newsweek |  5 November 2014
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