Human immunodeficiency virus (HIV) is an RNA virus that targets the immune system and is typically transmitted through sexual intercourse but also commonly through contact with infected bodily fluids as seen in blood transfusion, breastfeeding, and sharing of sharps. They are of two types – HIV1 & 2 and belong to the family of retroviruses. They typically invade the immune system, target and destroy the CD4+ T-lymphocytes, and ultimately make the body prone to attack by opportunistic pathogens. It is a chronic infection and currently has no cure.
The burden of HIV and HIV treatment
HIV is an epidemic, one that has been neglected since the COVID pandemic but embodies a major and enduring hazard to human health. According to the WHO, the global death toll of HIV is over 35 million and as of 2020, about 37.7 million people are living with it with an annual new infection rate of about 1.5 million.
Globally, 28.2 million people living with HIV are receiving ART in 2021. This, in 2020 amounts to about 73% of the global coverage rate. Billions of dollars are put into the production and distribution of these antiretroviral drugs.
Previous studies on HIV and limitations
Before the recent studies on gene editing, HIV studies relied on cells like HeLa (immortalized cancer cells). These cells were easy to manipulate but were not perfect representatives of the human blood cells. An important drawback of this study pattern is that it utilized technology to downregulate the expression of some genes but not shut them off completely as seen in the newer gene-editing studies and this posed the problem of uncertainties in the role of a gene in the upregulation or downregulation of viral replication.
Gene editing studies
Gene editing is an umbrella name for a group of technologies that allow scientists to modify an organism’s genome. With them, information can be added, removed, or modified at particular locations in the organism’s DNA. One of these is the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) used by researchers at Northwestern Medicine to unearth new information about the virus’ biology that portends benefits in the development of new treatment strategies. To answer the question of how the virus infects the human body, they, in a study published in the journal, Nature Communications, were able to identify 86 genes that may be implicated in the disease pathogenesis 40 of which have not until now, been thought of within the confines of HIV. With CRISPR an absolute state of the genes could be maintained – on or off, says Judd Hultquist, co-author of the study, and this was the game-changer.
In the study, T-lymphocytes were isolated from the human blood, and using CRISPR-Cas9 gene editing, several genes were “knocked out” before these cells were infected with the virus. These cells were analyzed and the results showed that cells with genes important for viral replication knocked off had decreased replication while the opposite is true for cells that had antiviral factors knocked off. Their findings were validated by selectively knocking out the isolated genes in new donors.
This study is proposing a new road map to the understanding of how viral DNA integration into host cells occurs. According to Hultquist, the current treatments for HIV are not curative, thus requiring individuals to adhere strictly to a lifelong regimen requiring access to affordable and good health care, and to him, it is not the world we should live in.
The study by scientists at Northwestern Medicine using CRISPR in the field of HIV virology is showing promising advancements in the direction toward a lasting cure. With it, a genome-wide screening to identify all the key players in the disease pathogenesis could potentially solve the puzzle crippling the development of effective therapies and hence, tilt us closer to a lasting solution.