Antibodies that block an entry pathway of Ebola are discovered

Antibodies that block an entry pathway of Ebola are discovered

Approximately half of the cases of Ebola, a serious hemorrhagic disease that does not have treatment, are fatal.

In the Democratic Republic of the Congo, in Africa, there is an epidemic of the virus (caused by the Zaire species) since August 2018 which, according to figures from the World Health Organization (WHO).

Has already killed 1,281 people out of the 1,920 diagnosed with this disease. Finding a vaccine against Ebola is the main objective of many researchers.

Now, a team from the Institute of AIDS Research IrsiCaixa, jointly promoted by La Caixa and the Ministry of Health, has discovered that filoviruses (a family of viruses that encompass Ebola)

Share with HIV one of the entry routes to Myeloid cells of the immune system, and have designed antibodies, still in the preclinical phase, that completely block this pathway in human cells.

There are many more entry ways, but this is one of them. This work was just published in the journal ‘Nature Microbiology’.

The difficulty of designing therapies against Ebola is that you can not predict which species of the virus will emerge in each block

The main obstacle when designing therapies against viruses of great genetic variability, such as HIV, is the need to act simultaneously against multiple targets of the virus so that the treatment does not lose effectiveness.

In the case of Ebola, the complexity arises because you can not predict which species will emerge in each outbreak.

One way to avoid this pitfall is to design a therapy against viral receptors in the cell [or, what is the same thing, the ways of entry of the virus],” explains Nuria Izquierdo-Useros, associate researcher at IrsiCaixa and co-leader of the article.

“But for that we have to know what those receptors are, and now we have found a new one and designed different antibodies that can block it,” he adds.

The Siglec-1 protein

The work has shown that viruses of the family ‘Filoviridae’, which encompasses the different species of Ebola and other viruses that cause hemorrhagic fevers (such as, for example.

Marburg) use the Siglec-1 protein to penetrate myeloid cells of the immune system, which are responsible for initiating the defense response of the organism against an infection.

Siglec-1 is the same doorway that HIV uses to invade these cells, and was discovered in 2012 by the same team of researchers, the Retrovirology and Clinical Studies group of IrsiCaixa.

In this study, scientists have worked with Virus-LikeParticles (VLP) of Ebola, which are synthetic viral particles that mimic the structure of the virus but do not have their infectious capacity, so they can be safely manipulated in laboratories.

Thus, they have shown that antibodies block the entry of Ebola into myeloid cells, experimenting with dendritic cells, monocytes and immune cells of the lymphoid tissue.

These are the first cellular targets affected by the virus, before expanding into other organs and tissues.

According to Daniel Perez-Zsolt, researcher at IrsiCaixa and first author of the work, the key to the new antibodies is that “they would be useful regardless of the species of the virus that emerged”.

“We have been experimenting with VLP of the Zaire species of the Ebola virus and with VLP of the Marburg virus, and on all occasions we see a blocking effect”.

At the same time, the study has found that “other receptors that were supposed to have an important role do not have such a clear contribution in the infection of the myeloid cells of the immune system.”

The next step, the scientists point out, will be to test the antibodies with real viruses in animal models and in laboratories of level 4 of biosafety, the maximum existing and necessary to work with a virus of the infectious capacity of Ebola.

If the results are confirmed, the antibodies could be used to prevent or treat the infection, in combination therapies with other drugs because Siglec-1 is not the only route of entry into the cells.

An antiviral against Ebola has to be effective against all the entry doors of the virus, and these have not yet been fully identified, we must close all the entry routes, and we have already achieved it with one,” he says.

ICREA researcher at IrsiCaixa and leader of the group that has done this work.



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