HIV-infected H9 t-cell. Credit: NIAID
MitoQ, an openly available dietary supplement that acts as a mitochondrial anti-oxidant, was found through a mouse study to counteract the damaging impacts that HIV and antiretroviral treatment (ART) cause on the mitochondria within the brain, heart, aorta, lungs, kidney, and liver.
The research team used a molecular technique to calculate the percentage in between human and murine mitochondrial (mtDNA) and nuclear DNA (ntDNA), an essential indication of mitochondrial dysfunction. A decrease in this ratio signals impaired mitochondrial function. Relative to their healthy equivalents, mice contaminated with HIV and treated with ART showed mitochondrial dysfunction in human immune cells across various organs consisting of the brain, heart, liver, lungs, and gut.
ART itself also affected mitochondrial function in mouse heart cells. When treated with MitoQ for 90 days, HIV-infected mice had decreased mitochondrial dysfunction in organs compared to HIV-infected mice on ART.
Relative to their healthy equivalents, mice infected with HIV and treated with ART showed mitochondrial dysfunction in human immune cells throughout various organs including the brain, heart, liver, lungs, and gut.
The factors for this are unclear, but it is understood that mitochondrial dysfunction contributes to organ damage and is present in persistent HIV. The scientists used humanized mice, which have human immune cells that can be infected with HIV. “Our findings support medical trials of MitoQ in individuals with HIV who take antiretrovirals to identify whether it can be a prospective treatment for comorbidities associated with persistent HIV infection. Up until then people with HIV must not take this diet plan supplement for treatment of any conditions associated with HIV infection.”
Background
Mitochondria are the crucial cell structures that are essential for the smooth function of organs such as the brain, kidney, heart, and liver. HIV triggers a persistent state of inflammation and immune dysfunction that contribute to organ damage organs. The reasons for this are uncertain, however it is known that mitochondrial dysfunction adds to organ damage and exists in persistent HIV. There are no therapies for HIV-associated diseases that affect organs such as the heart, brain, and liver.
Methodology
The scientists utilized humanized mice, which have human immune cells that can be contaminated with HIV. They contaminated them with the virus, treated them with ART including tenofovir disoproxil raltegravir, fumarate, and emtricitabine, then fed them MitoQ through drinking water for three months. The control mice were not provided MitoQ.
The scientists keep in mind that humanized mice do not precisely recreate HIV infection in humans. Likewise, the contaminated mice were exposed to both the art and the infection and they could not dissect the precise contribution of the virus versus the ART to mitochondrial dysfunction in human cells.
Impact
These preclinical findings might function as the foundation for scientific trials in human beings with HIV.
Commentary
” MitoQ is a diet plan supplement that is known to be safe in human beings and is easily offered for use,” said senior author Dr. Theodoros Kelesidis, associate professor of medicine in the department of transmittable diseases at the David Geffen School of Medicine at UCLA. “Our findings support clinical trials of MitoQ in individuals with HIV who take antiretrovirals to figure out whether it can be a potential treatment for comorbidities related to chronic HIV infection. Till then people with HIV must not take this diet supplement for treatment of any conditions associated with HIV infection.”
Recommendation: “Mitoquinone Mesylate and Mitochondrial DNA in End Organs in Humanized Mouse Model of Chronic Treated Human Immunodeficiency Virus Infection” by Sihyeong Song, Sandro Satta, Madhav B Sharma, Cristelle Hugo, Athanassios Kossyvakis, Shubhendu Sen Roy and Theodoros Kelesidis, 24 March 2023, The Journal of Infectious Diseases.DOI: 10.1093/ infdis/jiad044.
The research study was moneyed by the National Institutes of Health, the California HIV/AIDS Research Program, and the Campbell Foundation.