Previous studies show that HIV-1 utilises host-encoded proteins to facilitate its replication. Although HIV is a single-stranded RNA virus, after it infects an immune cell it is rapidly reverse transcribed into DNA, increasing the level of DNA found in the fluid portion of a cell, known as cytosol. Elevated cytosolic DNA triggers a sensor called STING, a stimulator of interferon genes, which turns on the innate immune response. It is, therefore, of great significance to understand the roles of proteins in viral replication and innate immune response induction by HIV-1 infection. The current study expands the understanding of the role of host proteins in viral replication and the innate immune response to HIV infection.
The current study shows that the host protein NLRX1 is responsible for HIV infection and works by repressing the innate immune response. Results show the reduction of HIV-1 infection in NLRX1 depletion cells is due to an impaired nuclear import of HIV-1 DNA. Data findings show that NLRX1 promotes HIV-1 infection by attenuating reverse-transcribed, HIV-1-DNA-induced IFN-I, IFN stimulatory genes, and proinflammatory cytokines.
Results show that NLRX1 interacts directly with STING, essentially blocking its ability to interact with an enzyme called TANK-binding kinase 1 (TBK1). Data findings show that the STING-TBK1 interaction is a critical step for interferon production in response to elevated cytosolic DNA, and initiates the innate immune response.
The lab explain that the innate immune response works by producing a cascade of signaling chemicals, namely interferons and cytokines, which trigger cytotoxic T cells to kill pathogens. They go on to add that increasing evidence suggests that mounting an early, potent innate immune response is essential for the control of HIV infection, and may improve the effectiveness of vaccines. Importantly, results show that deficiencies in NLRX1 reduce HIV replication, suggesting that small molecules to modulate the innate immune response may inhibit viral transmission and promote immunity to infection.
The team surmise that their findings showing NLRX1 reduces the immune response to HIV is similar to the discovery of host immune checkpoints, such as PD-L1 and CTLA-1, that control the immune response to cancer. They go on to add that immune checkpoints are immunological ‘brakes’ that prevent the over-activation of the immune system on healthy cells; tumour cells often take advantage of these checkpoints to escape detection of the immune system. For the future, the researchers state that checkpoint inhibitors have made a huge impact on cancer treatment and conclude their study, showing that NLRX1 is a checkpoint of STING, sheds more light on the topic and will help advance those efforts.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.
Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.
Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.
Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.