Study probes protein that may block HIV

“Scientists have shown how some cells in the body can repel attacks from HIV by starving the virus of the building blocks of life,” BBC News has reported.

The news is based on a study that had discovered how some cells may restrict HIV infection. The study looked at why a protein called SMADH1 was able to help certain immune system cells resist the HIV virus, with researchers finding that the body uses the protein to break up the building blocks of DNA, called dNTPs. This is of interest as the HIV virus spreads by initially constructing DNA segments from dNTPs. This DNA is then inserted into our normal DNA sequence, tricking the body into making HIV particles and spreading the infection.

However, the SAMHD1 protein appears to restrict HIV infection by reducing levels of dNTPs needed for it to initially make DNA segments. The researchers predict that lowering levels of dNTPs could therefore be a general mechanism for limiting infection by any organism that needs to make DNA in order to replicate.

This interesting research demonstrated how some cells can resist HIV infection. However, HIV targets a type of immune cell called a ‘T cell’ that has low levels of SAMHD1 and high levels of dNTPs. In addition, the ability to translate this finding into a therapy is hampered by the fact that many cells, including T cells, are continually dividing and therefore need dNTPs to replicate their own genetic material.

Where did the story come from?

The study was carried out by researchers from scientific and medical institutions in France, the US and around the world, including the Institut Cochin, Centre National de la Recherche Scientifique and the Université of Paris Decartes, the University of Rochester Medical Center, and the New York University School of Medicine.

The study was funded by a number of charitable, academic and governmental research organisations, including the US National Institutes of Health and the European Research Council. It was published in the peer-reviewed scientific journal Nature Immunology.

This story was well covered by the BBC.

What kind of research was this?

This was a laboratory study that used purified protein and cells grown in cultures to investigate the role of a protein called SAMHD1 in HIV infection.

SAMHD1 is a protein that is thought to play a role in immune responses and the amount of SAMHD1 produced varies between different types of immune cells. For example, immune cells like dendritic cells (or antigen-presenting cells) have high levels of SAMHD1, while other immune cells like T cells have low levels. SAMHD1 restricts the infection of dendritic cells by HIV.

This study aimed to determine the mechanism through which SAMHD1 might restrict HIV infection. This is the most appropriate study design to explore this question.

What did the research involve?

The researchers performed a number of experiments to determine the role of SAMHD1:

• they examined the effect of reducing SAMHD1 levels in cells grown in culture
• they purified SAMHD1 and looked at whether it could break up dNTPs
• they looked at the effects of introducing SAMHD1 to cells that do not normally produce it
• they looked at the ability of HIV to infect cells when SAMHD1 was and was not present

What were the basic results?

Through their experiments the researchers found that SAMHD1 breaks up the building blocks of DNA, called deoxynucleoside triphosphates (dNTPs). In order to spread, HIV needs to replicate its genetic material inside host cells by producing DNA. SAMHD1 was found to restrict HIV’s infection process in cell samples by reducing levels of dNTP molecules, meaning the virus cannot make the DNA necessary for replication.

How did the researchers interpret the results?

The researchers conclude that ‘by depleting the pool of available dNTPs, SAMHD1 effectively starves the virus of a building block that is central to its replication strategy.’ They add that depleting the pool of available nucleotides could be a general mechanism for protecting cells from infectious agents’ that make DNA.

Conclusion

This interesting research has shown that a protein called SAMHD1 breaks up DNA buildings blocks (dNTPS). This limits HIV infection in cells that express high levels of SAMHD1, like the immune system’s dendritic cells (antigen presenting cells). The researchers conclude from their lab tests that reducing the levels of dNTPs could potentially protect cells from any infectious agent that needs to make DNA.

However, while this laboratory based study has found some rather intriguing results, the ability to translate its finding into a therapy for limiting infection is hampered by one key fact: DNA reproduction is an important process constantly performed within our bodies as our cells replicate. It therefore remains to be seen whether we can harness this defensive mechanism as a way to fight HIV or other viral infection without negatively affecting vital processes in the body.