Human cells have an intrinsic capacity to destroy HIV. However, the virus has evolved to contain a gene that blocks this ability. When this gene is removed from the virus, the innate human immune system destroys HIV by mutating it to the point where it can no longer survive.
This phenomenon has been shown in test tube laboratory experiments, but now researchers at the University of North Carolina School of Medicine have demonstrated that the same phenomenon occurs in a humanized mouse model, suggesting a promising new target for tackling the virus, which has killed nearly 30 million people worldwide since it first appeared three decades ago.
A family of human proteins called APOBEC3 effectively restrict the growth of HIV and other viruses, but this action is fully counteracted by the viral infectivity factor gene (vif) in HIV. In the study, researchers intravenously infected humanized mice with HIV. They found that the most commonly transmitted strains of HIV are completely neutralized by APOBEC3 proteins when vif is removed from the virus.
Without the vif gene, HIV can be completely destroyed by the body's own immune system, says J. Victor Garcia, PhD, professor of medicine at the UNC School of Medicine and senior author on the study. These results suggest a new target for developing drugs fully capable of killing the virus.
Garcia and his colleagues pioneered the humanized mouse model used for these studies. The aptly named BLT mouse is created by introducing human bone marrow, liver and thymus tissues into animals without an immune system of their own. The mice have a fully functioning human immune system and can be infected with HIV in the same manner as humans. In previous research, Garcia and his team have effectively prevented intravenous, rectal, vaginal and oral transmission of HIV in the mice with pre-exposure prophylaxis (PrEP).
For the current study, Garcia and his colleagues also infected BLT mice with another, highly harmful strain of the virus. The results show that this strain of HIV does continue to replicate, even without vif, but at a much slower rate and without harming the human immune system. Further, the researchers found that virus replication in this case was limited to one tissuethe thymusin the entire body.
Â
These findings demonstrate a fundamental weakness in HIV, said John F. Krisko, PhD, lead author on the study. If this weakness can be exploited, it might eventually lead to a cure for HIV/AIDS, Krisko says.
The study appears March 28 in the online journal PloS Pathogens.
In addition to Garcia and Krisko, other study authors are Francisco Martinez-Torres, PhD, and John L. Foster, PhD, all of the Center for AIDS Research at the University of North Carolina School of Medicine.
Source: University of North Carolina School of Medicine
Navigating the Confluence of Respiratory Pathogens: Preparing for the Winter Triple Threat
September 30th 2023Medical investigators are concerned about a triple threat this winter with COVID-19, influenza, and RSV. Vaccination is crucial, but distribution challenges remain. Wearing masks, hand hygiene, and ventilation is important to prevent infections. Hospitals need comprehensive plans to respond efficiently.
Low Vaccination Concerns Highlight Need for Fall and Winter 2023 Vaccination Campaigns
September 28th 2023Cases of COVID-19, RSV, and influenza are expected to rise this fall and winter season; yet, the number of people who plan on getting the vaccines for each of the infections remains low, according to the NFID announcement today.
Evolving Symptomatology: Respiratory Viruses in the Era of COVID-19 Variants
September 27th 2023As COVID-19 restrictions eased up, other respiratory viruses began circulating alongside SARS-CoV-2. It's crucial to identify cases and understand the symptoms of these infections to track the evolution of the virus and what health care workers should look out for.
Poll: What Minimum Educational Requirement Should Infection Preventionists Have?
September 25th 2023Many infection preventionists (IPs) disagree on the minimum requirement to have the IP position. Let Infection Control Today know your opinion. Answer this poll, and send your thoughts to Senior Editor Tori Whitacre Martonicz at tmartonicz@mjhlifesciences.com.
How to Prepare For Possible “Tripledemic” of RSV, Influenza, and SARS-CoV-2
September 25th 2023The interaction between the respiratory viruses SARS-CoV-2, influenza, and RSV, poses ongoing challenges. Personal protective measures, testing, and vaccination are critical components of our strategy to mitigate the impact of these viruses.
2 Clarke Drive
Cranbury, NJ 08512