Researchers support new strategies for HIV control

December 18, 2019

The search for a cure to AIDS has partly focused on ways to eradicate infected cells. Now, new research from Karolinska Institutet in Sweden and the University of Pennsylvania in the U.S. shows that this approach may not be necessary for a functional cure. In a study focusing on a subset of HIV-positive individuals who can live with the virus without needing treatment, the researchers found that these people's lymphocytes suppress the virus but do not kill off infected cells.

AIDS is a persistent global health issue with no existing vaccine or cure. HIV infection typically leads to a loss of CD4+ T cells, a type of white blood cells that together with the CD8+ T cells attack and destroy infections. The less CD4+ T cells a person has, the worse are the symptoms. But fewer than 1 percent of HIV-positive people have stable CD4+ T cell counts and undetectable HIV viremia and are thus able to live with the virus without therapy. This group, known as elite controllers, has more effective CD8+ T cells--the cells that kill off viruses--than most HIV-positive people.

In this study, published in Science Translational Medicine, the researchers wanted to find out exactly how the CD8+ T cells of elite controllers keep the HIV virus from replicating and progressing to AIDS. They collected blood samples and lymph node tissue biopsies of a total of 51 HIV-positive individuals, including 12 elite controllers, from three different sites in the U.S. and Mexico.

Using single-cell RNA sequencing analyses, a method used to study individual cells, the researchers found that elite controllers had more HIV-specific CD8+ T cells in their lymphoid tissue than the others but that these were so-called non-cytolytic cells, meaning they didn't kill off infected cells. Instead these CD8+ T cells of elite controllers had a distinct transcriptional profile and were able to suppress HIV replication through an enhanced ribosomal function, meaning they were better at translating proteins from amino acids. This led to the production of more and a greater variety of cytokines, small protein molecules that are important in cell communication, and boosted the cells' polyfunctionality.

"These findings go against the paradigm of HIV control that focuses on killing off infected cells to find a cure," says Marcus Buggert, assistant professor at the Department of Medicine, Huddinge, at Karolinska Institutet. "While these strategies may still work, our research supports a model in which viral suppression rather than viral eradication can in fact serve as a functional cure."
The study was funded, in part, by Swedish Research Council, Karolinska Institutet, Swedish Society for Medical Research (SSMF), the Jeansson Foundations, the Åke Wiberg Foundation, the Swedish Society of Medicine, Läkare Mot AIDS Forskningsfond, the Magnus Bergvall Foundation, the Lars Hiertas Foundation, Oregon National Primate Research Center, NCI, the NIH, the Penn Center for AIDS Research, the Campbell Foundation, the W.W. Smith Charitable Trust, the BEAT-HIV Delaney Collaboratory, the Wellcome Trust, the University of California, San Francisco (UCSF)-Gladstone Institute of Virology and Immunology Center for AIDS Research, the Delaney AIDS Research Enterprise and the amfAR Institute for HIV Cure Research.

Publication: "Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells," S. Nguyen, C. Deleage, S. Darko, A. Ransier, D. Truong, D. Agarwal, A. S. Japp, V. H. Wu, L. Kuri-Cervantes, M. Abdel-Mohsen, P. M. Del Rio Estrada, Y.Ablanedo-Terrazas, E.Gostick, J.A. Hoxie, N. R. Zhang, A. Naji, G. Reyes-Terán, J. D. Estes, D. A. Price, D. C. Douek, S. G. Deeks, M. Buggert, M. R. Betts, Science Translational Medicine, Dec. 18, 2019.

Karolinska Institutet

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to