In cooperation with a team from the Walter Reed Army Institute of Research in the USA, researchers from the Ulm University Medical Centre have been successful in identifying an antiviral factor for the first time through single-cell analysis in blood samples of HIV patients. Though many antiviral mechanisms have been already described, it is not clear which cellular factors in fact control the human immunodeficiency virus 1 (HIV-1) in afflicted individuals. The international team was able to demonstrate that effective production of the cellular protein prothymosin alpha (PTMA) correlates with a reduced production of HIV-1 in the blood cells of patients. The results were published in the renowned journal "Science Translational Medicine”.
The scientists examined patient samples from the acute and chronic phases of an HIV infection. Using the method of single-cell transcriptome analysis, they investigated how the expression of genes in the host cells relates to the amount of viral RNA in the individual cells. The results suggested that the cellular protein PTMA restricts the transcription and replication of HIV-1. The Ulm doctoral students Alexandre Laliberté and Caterina Prelli Bozzo, under the supervision of Professor Frank Kirchhoff, one of the heads of the Institute of Molecular Virology at the Ulm University Medical Centre, were able to confirm this in cell-culture experiments and mechanistic studies. “Our results indicate that prothymosin alpha plays a key role in the body’s own defence against HIV”, explains Professor Frank Kirchhoff. In the long term, this could lead to the development of new antiviral therapies.
Recovery obstacle
The inhibition of HIV transcription plays an important role in the latent infection of long-lived, so-called memory T cells. In this dormant form, the virus is barely detectable to the immune system and medication, but it can become active again if the HIV therapy is interrupted. The latent HIV infection of memory T cells thus presents a major treatment obstacle. Blocking PTMA could enable the activation of these dormant viruses, to make them vulnerable and improve treatment strategies.
This research was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) within the scope of the Collaborative Research Centre 1279 “Exploiting the human peptidome for novel antimicrobial and anti-cancer agents” and the Baden-Württemberg Foundation. Cooperation partners were the teams of Dr Rasmi Thomas (Walter Reed Army Institute of Research, Silver Springs, Maryland, USA) and Professor Beatrice H Hahn (University of Pennsylvania, Philadelphia, USA).
Publication reference:
Aviva Geretz, Philip K Ehrenberg, Robert J Clifford, Alexandre Laliberté, Caterina Prelli Bozzo, Daina Eiser, Gautam Kundu, Lauren K Yum, Richard Apps, Matthew Creegan, Mohamed Gunady, Shida Shangguan, Eric Sanders-Buell, Carlo Sacdalan, Nittaya Phanuphak, Sodsai Tovanabutra, Ronnie M Russell, Frederic Bibollet-Ruche, Merlin L Robb, Nelson L Michael, Julie A Ake, Sandhya Vasan, Denise C Hsu, Beatrice H Hahn, Frank Kirchhoff, Rasmi Thomas. Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo. Sci. Transl. Med.15, eadg0873 (2023).
DOI: doi.org/10.1126/scitranslmed.adg0873
Further information:
Prof Dr Frank Kirchhoff, co-director of the Institute of Molecular Virology at the Ulm University Medical Centre, email: frank.kirchhoff[at]uni-ulm.de
Text a mediacontact: Christine Liebhardt
Translation: Kate Gaugler