In the vast majority of cases, individuals infected with the human immunodeficiency virus (HIV) go on to develop acquired immune deficiency syndrome (AIDS) and ultimately die if left untreated. However, a small number of people, around 1%, are able to control HIV replication effectively without drugs, so much so that the virus remains undetectable for extended periods of time. These individuals are known as “elite controllers (ECs),” and are of particular interest because they may guide the development of treatments and vaccines, and also provide models for a cure of HIV.
That’s why a group of French scientists from the Institute of Health and Medical Research decided to scrutinize the genomes of two ECs, in the hope that they could find viral or host factors contributing to this phenomenon.
As described in the journal Clinical Microbiology and Infection, the patients had both been diagnosed as HIV positive, but displayed no HIV-related disease. Furthermore, standard tests for HIV DNA couldn’t pick up any traces of the virus. Using more sophisticated sequencing techniques, the researchers were able to retrieve the HIV sequences that had been integrated (inserted) into their genomes; integration occurs in all HIV infected individuals.
They found that the virus had been inactivated by a series of mutations that resulted in the insertion of lots of “stop” signals that continually halted replication. They also found that a group of antiviral host enzymes called APOBEC, which are usually inhibited by the virus, demonstrated increased activity from very early on in the infection.
From these results, they believe that this “cure” could be explained by spontaneous evolution between the virus and the host, leading to a process called “endogenization.” Endogenization is where viruses become part of the genetic material of their host species, leaving behind mostly nonpathogenic remnants of the infection called endogenous retroviruses (retroviruses are a family of viruses that includes HIV). This process has been observed for many other HIV-related viruses in mammals, and some 8% of our genome is known to be composed of endogenous retroviruses.
Rather than clearing HIV from the body, which is what treatments strive to achieve, the researchers propose that an HIV cure could occur through endogenization if the endogenized virus eventually becomes fixed in the population. “We suggest that persistence of integrated HIV DNA is not a barrier, but on the contrary, may be a prerequisite to HIV cure,” said the authors. They also believe it may eventually be possible to target the APOBEC enzyme in order to induce a similar response, opening up new treatment avenues.
However, this research should be treated with a healthy dose of skepticism. “If it came across my desk for review, it would get short shrift, to be honest,” University of Nottingham molecular virology professor Jonathan Ball told AFP. He said that the researchers had zero evidence of a functional cure for HIV, so be wary of misleading headlines. Furthermore, Ball points out that endogenization can only occur when the virus is passed onto offspring via sperm or eggs (gametes). “I am not aware at all of them showing the presence of the virus in any gamete,” he added.
While this research is useful in understanding the complex interplay between the virus and host, it will be a long time before the results can be translated into treatments or possible cures.