In a new study, researchers described a discovery that violated the rules of the game in this field. Their research results show that a host protein family, which has long been considered as a pure antiviral substance, sometimes helps latent HIV find a safe harbor in patients.

 

Understanding HIV latency at the molecular level is crucial for efforts to eliminate the virus scourge that causes immune deficiency syndrome (AIDS, commonly known as AIDS). Latent infection cell bank (also known as HIV virus bank) – HIV hides and persists in the body of infected patients in a silent standby mode – is the reason why antiretroviral therapy (ART) has never eliminated this virus. In short, these latent HIV virus banks are the biggest obstacle to curing this disease.

 

Now, in a new study, researchers from the University of Ottawa and the University of Western Ontario in Canada described an unconventional discovery that might change the rules of the game in this field. It may point the way forward for HIV cure research. Their research results show that a host protein family, which has long been considered as a pure antiviral substance, sometimes helps latent HIV to find a safe harbor in patients. The relevant research results were published in the journal Nature Communications, with the title “Antiviral APOBEC3 cyclidine deaminases alter HIV-1 virus integration site profiles”.

 

 

In this project, which began in 2016, Dr. Marc-Andr é Langlois, a virologist at the University of Ottawa School of Medicine, and his collaborators used cutting-edge technologies and testing methods to describe the impact of a host-encoded protein family called APOBEC3. These proteins have the powerful ability to mutate viral DNA and limit retroviruses such as HIV and other types of viruses. But their latest findings show that these proteins can play another role in addition to their traditional evolutionary role, and are not always beneficial to patients.

 

Dr. Langlois said, “We have shown a new mechanism through which HIV can become a latent virus – it can become a latent virus by acting on the host protein designed to protect us. But in fact, these proteins can ultimately help the virus to remain hidden in the body.”

 

He said, “This is an important discovery, because these proteins are always considered to be the protectors on our side. But our research shows that in some cases, they seem to have unexpected consequences, one of which is to help HIV enter the incubation state. HIV incubation is the biggest obstacle to curing it.”

 

This raises some important questions: Is the role of these proteins ultimately more beneficial or more counter-productive for HIV, a virus that tends to have a latent phenotype? Can a drug be developed to prevent the action of APOBEC3 protein, thus reducing the cell bank of HIV latent infection? These are the exploration contents that Dr. Langlois and his team will continue to study.

 

Dr. Langlois said, “Yes, we can use ART drugs to strictly control HIV, and these drugs have very good effects. But they are not a cure. We are trying to find a cure. We believe that part of the response after exposure will be to block the activity of APOBEC3 protein to inhibit HIV incubation. We have confirmed for the first time that this mechanism – a mechanism that is not paid attention to and contrary to mainstream thinking – is really happening. So this is the first layer of evidence It is reported that we will conduct follow-up research on this basis. “

 

In this new study, Dr. Langlois and his team focused on infection experiments. They provided samples to the collaborators of the University of Western Ontario, who provided the professional knowledge of “virus deep sequencing” and mapped the location of the virus inserted into the human genome after infection.

 

Since this mechanism has been confirmed in vitro in the laboratory and to some extent in patient samples, Dr. Langlois hopes to promote it to a new level through animal models. Although the overall impact of APOBEC3 protein on the characteristics of HIV integration sites is not clear at this stage, his research team is committed to exploring potential answers.

 

The risk of such research is high. Since the emergence of HIV/AIDS as a new immunodeficiency syndrome in the early 1980s, HIV/AIDS has been one of the most serious health challenges in the world. Significant progress has been made in the fight against this virus. However, there are more than 38 million HIV-infected people in the world, and tens of millions of people have died of HIV-related diseases since the beginning of the epidemic.

 

 

Reference

Hannah O. Ajoge et al. Antiretroviral APOBEC3 cytidine deaminases alter HIV-1 provirus integration site profiles. Nature Communications, 2023, doi:10.1038/s41467-022-35379-y.