Genes affecting HIV infection identified using CRISPR genome editing

Genome editing of blood could provide new treatments for HIV according to a new study.

A research team from Northwestern University, Illinois, has identified specific genes needed for HIV to infect the blood. The team used CRISPR/Cas9 genome editing to switch off individual genes, known as 'knocking out' a gene, and observed how this affected HIV infection. The study demonstrated a new way of understanding how HIV could cause long-term infection and the treatments that could emerge from this.

'The existing drug treatments are one of our most important tools in fighting the HIV epidemic and have been amazingly effective at suppressing viral replication and spread,' said Dr Judd Hultquist, co-corresponding author from Northwestern University. 'But these treatments aren't curative, so individuals living with HIV have to follow a strict treatment regimen that requires continual access to good affordable health care – that's simply not the world we live in.'

Publishing their findings in Nature Communications, the scientists took cells that HIV most commonly infected, T cells, from human blood donations and knocked genes out in these samples. Viruses replicate by 'hijacking' the host's DNA, so the researchers wanted to identify which genes in the T cells were important for viral replication. The T cell samples were then infected with HIV and they discovered that when a gene important for viral replication was knocked out there was a decrease in infection. In contrast, when an antiviral gene was knocked out there was an increase in infection.

Of the 364 knocked out genes, the study found 86 genes that could alter HIV infection. Nearly 40 of these genes were not previously associated with HIV replication. The genes provided a source of potential host factors that could help scientists understand the mechanics of HIV replication in T cells.

'That nearly half of the genes we found were previously discovered increases confidence in our dataset. The exciting part is that over half – 46 – of these genes had never before been looked at in the context of HIV infection, so they represent new potential therapeutic avenues to look into.' Dr Hultquist explained.

In previous studies, an immortalised cell line was used as a model to study the replication of HIV. But gene expression was only turned down in these studies, not switched off completely. As a result, it could not be said with certainty that any specific gene was involved in suppressing viral replication. However, using the CRISPR genome editing approach, scientists are able to switch genes on or off.

'With the CRISPR system, there's no intermediary – the gene is on or off. This capability to turn genes on and off in cells isolated directly from human blood is a game-changer; this new assay is the most faithful representation of what's happening in the body during HIV infection that we could easily study in the lab.' Dr Hultquist added.

The team stated that if the knowledge around how HIV multiplies improves, treatments for HIV could one day becomes cures.