Researchers map HIV infection by analysing individual cells of patients 

Researchers have mapped the effects that an HIV infection has on specific cells and genes in the body.

They used advanced technology called “high-throughput single-cell RNA-sequencing”, or scRNA-Seq. Researchers use it to to take a detailed look at what happens in individual healthy and diseased cells while a person’s body is being infected by a virus or bacteria.    

Such detailed information helps them understand the different cell types and genes involved when  a virus such as HIV first enters a person’s body. They are also able to trace the roles and functions of each during an ongoing infection.

All of this information helps scientists pinpoint targets in the body for better medicines and potential vaccines. 

Researchers used the scRNA-Seq technology to study blood samples of four women taken before and after they became infected with HIV. The researchers could therefore compare in great detail what happened in uninfected and infected cells. It helped them to identify the processes and genes inside the cells that play a role in strengthening the immune system and fighting diseases.

The researchers built up a map of the cells, genes and processes that are involved within the first month of a patient being infected with HIV.   

They found that right after the patients were infected with the HIV virus, there were many blood cells that help improve immunity. Many of these reactions are already known to protect the body from viruses, bacteria and other objects that might enter it. 

The researchers identified different immune cell types, as well as some of the genes involved. They worked out what drove specific molecules to start fighting off a virus.

They said that the bodies of two of the participants spontaneously tried to control the virus by quickly making more cells able to kill off unwanted viruses and bacteria. More than two years later, the amount of virus in their bodies was still lower than that of the other two participants. Their bodies therefore naturally controlled the infection. This might mean that they will not in future suffer such severe infections or symptoms.

Previous studies showed that the immune systems of people with continuously low virus levels are better at controlling chronic, ongoing infections and their potential symptoms.

The current study provides one framework or concept which other HIV researchers can use when they try to understand the reaction of the body to infections. This information is available in great detail, because the researchers were able to study what happens within individual cells.

It helps to better explain how a person’s immune system continuously responds to an ongoing viral infection such as HIV.

The researchers hope that their findings will help efforts to develop successful vaccines and other control measures against HIV (which is still a big problem in Africa) as well study other viral and bacterial infections in greater depth.

Abstract

Cellular immunity is critical for controlling intracellular pathogens, but the dynamics and cooperativity of the evolving host response to infection are not well defined. Here, we apply single-cell RNA-sequencing to longitudinally profile pre- and immediately post-HIV infection peripheral immune responses of multiple cell types in four untreated individuals. Onset of viremia induces a strong transcriptional interferon response integrated across most cell types, with subsequent pro-inflammatory T cell differentiation, monocyte MHC-II upregulation, and cytolytic killing. With longitudinal sampling, we nominate key intra- and extracellular drivers that induce these programs, and assign their multi-cellular targets, temporal ordering, and duration in acute infection. Two individuals studied developed spontaneous viral control, associated with initial elevated frequencies of proliferating cytotoxic cells, inclusive of a previously unappreciated proliferating natural killer (NK) cell subset. Our study presents a unified framework for characterizing immune evolution during a persistent human viral infection at single-cell resolution, and highlights programs that may drive response coordination and influence clinical trajectory.

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