Parasites against HIV
Blood fluke eggs prevented HIV from infecting T‑lymphocytes
Maxim Abdulaev, N+1
The antigens contained in the eggs of schistosomes change the work of the immune system, preventing its cells from binding to HIV particles. In addition, it stimulates the growth of T cells, which are more resistant to the human immunodeficiency virus.
The study was published in the journal PLOS Pathogens (Mouser et al., Schistosoma mansoni soluble egg antigen (SEA) and recombinant Omega-1 modulate induced CD4+ T-lymphocyte responses and HIV-1 infection in vitro).
Schistosomes are parasitic flatworms that live in the blood and lay eggs in human veins. Schistosome eggs are able to fight the human immune system by releasing substances that alter the immune response. The main targets against which the substances of schistosome eggs work are dendritic cells. Substances secreted by parasites bind to the receptors of dendritic cells, preventing them from working normally.
Dendritic cells are needed by the immune system in order to introduce T cells (T lymphocytes) to the antigens of an invading infection. After the dendritic cells have brought antigens to the lymph nodes, different types of T cells are activated, which directly destroy the threat to the body - independently, or by activating B cells.
HIV infects T-cells. He can do this in two ways – cisinfect or transinfect them. In the first case, viral particles are directly attached to the membrane of T cells and penetrate inside. In the second method, they are brought to the T cells by dendritic cells to activate them, as with any other infection. But in the case of HIV, everything goes wrong – the virus passes from the surface of the dendritic cell to the lymphocyte and infects it. This means that it is possible to prevent the infection of T cells if you forbid the virus to attach to their receptors. This is exactly what the substances that secrete schistosome eggs do.
Esther C. de Jong from the University of Amsterdam, William A. Paxton from the University of Liverpool and their colleagues decided to test whether schistosomes could prevent dendritic cells from capturing HIV and transferring it to the lymph nodes to naive T cells. They made a drug from parasite eggs, which they called SEA (soluble egg antigen), and began testing it on dendritic cell receptors, the cells themselves, T-lymphocytes and HIV.
First, scientists conducted an experiment with the receptors of dendritic cells and the virus. They sustained the receptors in SEA and then in a viral protein solution. It turned out that SEA binds to dendritic cell receptors and leaves little room for viral receptors – SEA treatment reduced their binding to dendritic cell receptors by 70 percent.
Dendritic cell receptors bound to a viral protein analog in the presence of SEA (here and below are the figures from the article in PLOS Pathogens).
Then the scientists processed the SEA culture of dendritic cells, and then placed T-lymphocytes to it and began to infect them with HIV. It turned out that in an environment with treated dendritic cells, the virus develops 80 percent less.
The researchers isolated the omega-1 substance from SEA, the main component of the parasitic mixture, and tested it. In the experiment with him, the experimental scheme was slightly changed – now the dendritic cells treated with the fluke substance were in the same environment with naive T cells without the presence of a virus. Only after the T-lymphocytes were activated in the presence of the treated dendritic cells, the scientists transferred them and tried to infect HIV. It turned out that T-lymphocytes activated by treated dendritic cells are infected with HIV by 60 percent less. Scientists attribute this to the fact that under the action of omega-1, the activation of T cells occurs in such a way that the number of CCR5 receptors on their membrane decreases, which are necessary for the virus to bind to the lymphocyte.
The amount of viral protein in the culture of T cells infected with HIV. T cells are activated in the presence of omega-1.
In addition to the successes in this study, there are also failures. So, it turned out that the parasite's defense works only against a type of virus that uses the CCR5 receptor to enter the cell. HIV, which uses the CXCR4 receptor, does not notice any interference. In addition, the study was conducted only on HIV-1, and not both types.
The authors of the study believe that the results of the study should be taken into account when testing the HIV vaccine, if they are carried out in areas of schistosomiasis. In addition, according to the authors, vaccines developed on the basis of substances secreted by helminths can help in the fight against HIV.
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