Antiretroviral therapy (ART) has played a vital role in improving the health and life expectancy of people living with HIV. However, ART does not completely eradicate the virus. This raises the questions of where and how the virus persists in the body, and how it can best be targeted.
AHRI’s Dr Alex Sigal and his group have been awarded a five-year National Institutes of Health (NIH) Research Project Grant (R01) to help them find the answer to these questions.
The project, titled ‘Identification of the HIV Reservoir in Lymph Nodes Using Single Cell RNA-Seq’ will see the Sigal Group working with Alex Shalek from MIT – together with other collaborators.
Using lymph node samples from a cohort of patients on ART with undetectable viral loads, the scientists will use single cell RNA-Sequencing to identify cells which contain HIV transcripts. They aim to identify the precise cell(s)-of-origin for HIV maintenance and production in lymph nodes, by characterising each infected cell’s mRNA expression profile and its viral transcript levels. From this information they will be able to identify the cell types which harbour the virus in the face of therapy, as well as the host cell responses that may reveal the mechanisms underlying HIV persistence.
“The drugs are certainly working, there is not a question about that, it’s just that they are not getting rid of the last bit of infection. It’s this last little bit which can again form the seed of infection if you take the drugs away,” explains Dr Sigal.
The grant will also enable Sigal’s group to maintain and build on AHRI’s important clinical collaboration with surgeons from Durban’s Inkosi Albert Luthuli Central Hospital. This partnership means AHRI scientists have access to lymph node samples and other tissue samples discarded during surgery.
“Without knowing where and how the virus is hiding, we are unlikely to design a strategy that leads to a cure,” says Isabella Ferriera, a researcher on the study and a SANTHE trainee. “On the other hand, if the cellular source of the persistent HIV is found and it proves to be a very specific cell subset, we can potentially target the reservoir for elimination by targeting the host cells which harbour it.”
Top photo: Members of AHRI’s Sigal Group (l-r) Jessica Hunter, Alex Sigal, Isabella Ferriera and Sandile Cele, who will be working on the project.
By Phumla Ngcobo