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Exploring the Latest Breakthroughs in HIV Research

Groundbreaking research has uncovered several possibilities to potentially cure HIV in patients receiving antiretroviral therapy (ART), while a new drug prohibits the virus from maturing, preventing viral infection of new cells.

Groundbreaking research has uncovered several possibilities to potentially cure HIV in patients receiving antiretroviral therapy (ART), while a new drug was found to prohibit the virus from maturing, which would prevent viral infection of new cells.

For patients being treated for HIV, antiretroviral therapy can be life-changing. However, once treatment is stopped, dormant or latent cells infected with HIV can become reactivated. Previously, this made finding a cure for the disease nearly impossible; now, scientists from around the world have begun targeting these latent cells in their hunt for a cure.

Sugar-binding Protein as a Cure for HIV

Mohamed Abdel-Mohsen, PhD, staff scientist at Blood Systems Research Institute (BSRI), and associate specialist at the University of California at San Francisco (UCSF) School of Medicine, along with his colleagues, previously identified the human genes which contributed to the latency of HIV-infected cells. As an extension of that research project, Dr. Abdel-Mohsen and his colleagues from BSRI, UCSF, and the University of Hawaii have found that the human sugar-binding protein galectin-9 can expose latent HIV-infected cells, and ‘poison’ the virus, through a “shock and kill” strategy: by reactivating the latent cells, the immune system is able to detect HIV within the body and target it. This is done through the manipulation of certain classes of sugars found on the surface of HIV-infected cells, which then emit a signal that exposes the latent cells.

In addition, the group discovered that galectin-9 increased the levels of “APOBEC3G,” an antiviral protein. This protein has the ability to destroy viral genetic code, including that of HIV, meaning that galectin-9 has the potential to cure HIV infections. Dr. Abdel-Mohsen commented on the findings in a recent press release, “There's been very little attention paid to how the sugar coating on the surface of human cells affects the fate of the virus that lies inside. This sugar coating may hold the key to new therapeutics that can be harnessed to cure HIV and possibly a range of other infectious diseases.”

Dr. Abdel-Mohsen and Satish Pillai, PhD, lead study researcher, associate investigator at BSRI, and associate director of UCSF-Gladstone Institute of Virology & Immunology Center for AIDS research, agree that galectin-9 may provide an alternative to lifelong antiretroviral therapy as a means of HIV treatment, and may provide a means for a cure. Dr. Pillai stated, “Our findings make us optimistic that future HIV treatments can eliminate all traces of the virus from the body.”

ImmTAVs Protein as a Cure for HIV

In another study, headed by Professor Lucy Dorrell, MD, associate professor, senior clinical research fellow, honorary consultant at the Nuffield Department of Medicine, Oxford University, university researchers partnered with scientists from a biotechnology company in Oxfordshire, Immunocore Ltd, to “investigate the potency of novel engineered immune-mobilising T cell receptors-based drugs (‘ImmTAVs’), designed to clear HIV-infected cells,” according to a press release.

Like galectin-9, ImmTAVs exposes latent cells to the immune system, which then attacks and kills them, using what the researchers call the “kick and kill” approach. The two-headed protein ImmTAV can detect HIV protein cells through a genetically engineered T-cell receptor, and bind to CD3 T-cell co-receptors, which are found on the CD8+ T-cells that can kill infected cells.

ImmTAV was used on HIV-infected cells from patients who were successfully treated with ART. After using ImmTAV, researchers saw that the CD8+ T-cells killed latent CD4+ T-cells, the main immune system cell that is targeted by HIV, according to Professor Dorrell. When healthy CD8+ T-cells were used in addition to the ImmTAV treatment, “up to 85% of the infected cells were removed,” while the use of healthy CD8+ T-cells alone did not yield any effects, “confirming the essential role of the ImmTAV,” explained Professor Dorrell. She speculated, “This may be because, despite long-term ART, there is some degree of generalised malfunction in CD8+ T cells that has not been fully repaired.” She stated that ImmTAV cannot be a standalone cure for HIV, but can certainly play a key role in eradicating the virus.

HIV Drug Prohibits Infected Cells from Maturing

Researchers from the Molecular Medicine Partnership Unit, a collaboration between the European Molecular Biology Laboratory (EMBL) and Heidelberg University Hospital, are currently testing an inhibitor drug that can lock HIV-infected cells in immaturity by disallowing the virus from cutting the connection between the capsid protein and the spacer peptide 1. With this, the virus cannot spread to uninfected cells.

Earlier forms of the drug did not affect viruses that had certain mutations that enabled it to destabilize the immature structure. This permitted the virus to rearrange itself, exposing the virus’s cutting machinery.

Using cryo-electron tomography with subtomogram averaging, the researchers were able to view 3-D images of immature HIV cells. Doing so allowed them to identify all instances of the virus’ cutting point. This approach has enabled the group to study the details of the virus without having to purify it in the lab.

The researchers found that the virus’s cutting machinery are hidden. This discovery is important considering that the virus has to cut the connections between its building blocks and rearrange the pieces before it can mature and spread throughout the body. Florian Schur, predoctoral fellow at EMBL, explained that the inhibitor drug locks the viral structure in its immature form so that it cannot be cut.

HIV remains one of the most threatening viruses circulating the globe. However, the unconventional approach that recent researchers have taken to targeting the virus may be the key to eradicating it once and for all.