HIV can be stopped, suggests a new study published in the journal Molecular Therapy. The replication of the deadly virus can be shut down, and it can even be removed from the genetic material of infected cells by a simple gene editing strategy.
HIV infection remains without a known cure. Once infected, a person is to carry the virus till his death. Treatment methods do exist, but they only relieve the patient from some of the negative effects. Scientists are always trying to find a method to get rid of this problem completely, but they have not been able to find an effective solution. Now, here’s the good news: for the first time ever, HIV DNA has been removed from the genomes of living animals, thus eliminating the possibility of the virus infecting other cells. Such a feat has been accomplished by a team of researchers from the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh.
Normally, the virus, once it has entered the body of its host, will use the machinery of the latter’s immune cells to replicate itself. It will, then, remain hidden in the body for a long period of time when the infected person will not even feel any symptom. Throughout this latency stage, the virus will continue to replicate. The virus also embeds its DNA into the genomes of the infected person.
All of this can be prevented through a powerful gene editing technique called CRISPR/Cas9 which was applied on three animal models.
This work was based on a previous research conducted by the same team: back in 2016, they had demonstrated the deletion of specific pieces of HIV-1 from the genome of transgenic rat and mouse models whose genome was made to carry the virus’ DNA in all tissues—these findings have now been confirmed with the new study, which is deemed more comprehensive, explains lead author, Wenhui Hu, as their gene editing methodology was more refined. Also, Hu and his colleagues used two more mouse models, one representative of mouse cells with acute infection, and the other representative of human immune cells with chronic (latent) infection (these ‘humanised’ mice has human immune cells transplanted into their tissues).
Firstly, HIV-1 was genetically inactivated in transgenic mice: this lowered the amount of RNA expression of the genes of the virus by as much as 95%. Then, acutely-infected mice with a mouse HIV-equivalent (EcoHIV) were tested with the strategy; acute infection is characterised by active replication of HIV. The CRISPR/Cas9 strategy was shown to inhibit viral replication in EcoHIV mice, thereby possibly avoiding infection throughout the body (systemic infection), explains co-author Khalili. The excision efficiency was recorded at 96% in these mice. This is the first evidence for the destruction of HIV-1 with a CRISPR/Cas9 system.
The humanised mice (those bearing human immune cells) had latent HIV in their human T cell genomes; in this way, the virus normally evades detection from the body, a strategy that boost the virus capability to flourish. However (and thankfully), a single treatment with the CRISPR/Cas9 system was enough to excise viral pieces from the infected human cells in the mice.
This study is described as an important step towards the development of a permanent cure for HIV infection. The next phase will now be to reproduce these results in primates, which constitute a more reliable animal model for humans. Khalili says that their long-term goal is to start clinical trials with human participants.