Research on the Spanish-Italian family immune to HIV published in prestigious medical journal PLOS PATHOGENS

The Conquistado Escalones Association is formed by a Spanish-Italian family that suffers from a degenerative, muscular and hereditary disease called Limb-girdle Muscular Dystrophy 1F (LGMD1F) for 8 generations. Currently and despite their health and mobility problems, they do not cease to carry out campaigns and events to pay for research that seeks a cure for them and thanks to the discovery made in recent years, a possible and new way to stop HIV infection .

Researchers from the Carlos III Health Institute have led an investigation that is published this Thursday in the prestigious magazine Plos Pathogens and that describes a genetic defect in the gene of Transportin 3 which is the cause of this Limb-girdle Muscular Dystrophy 1F and in turn protects against HIV infection.

The published study of which Dr. Sara Rodriguez-Mora is the first signatory and correspondence authors are Dr. Mayte Coiras and Dr. José Alcamí, researchers at the AIDS Immunopathology Unit of the Carlos III Health Institute, is part of an international consortium of which are part the Hospital La Fe in Valencia led by Dr Juan Jesús Vilchez, the group of Dr Zeger Dbyser of the University of Leuven in Belgium and Dr. Rubén Artero of the University of Valencia. This project has been funded in large part thanks to the crowdfunding by the affected patients of “Conquistando Escalones Association” and the PRECIPITA platform. The MERCK SALUD Foundation and the Strategic Health Action of the Carlos III Institute have also contributed to the financing of the project.

Transportin 3 is a cellular protein that, as its name describes, has the function of transporting proteins between the cytosol and the cell nucleus. In 2008 a series of works showed that this protein is essential for HIV infection. Subsequently, researchers from the Vall d´Hebrón hospitals in Barcelona and La Fe in Valencia described that patients with a rare muscular disease – limb-girdle muscular dystrophy 1F, LGMD1F in its acronym in English – that affects a single family in Spain and Italy were carriers of a mutation in the Transportin 3 gene.

Researchers at the AIDS Immunopathology Unit of the Carlos III Health Institute proposed the hypothesis that due to this mutation the affected patients would be resistant to HIV infection. This hypothesis has been confirmed and the mechanism that blocks HIV infection is described in the published article. This is the second genetic mutation in history that protects against HIV infection.

Transportin 3 acts at various levels in the HIV cycle, cytosolic transport of the capsid, transport to the nucleus and the integration of the virus genome into cellular DNA. The results obtained suggest that in patients carrying the mutation, transport to the nucleus and integration are profoundly altered.

“Viruses carry genetic information necessary but not sufficient to complete their replicative cycle. They need cell proteins for this and they become parasites that adapt to the cell pathways that allow them to multiply. Among the proteins to which they adapt are those that regulate intracellular transport. HIV has adapted to using Transportin 3, a molecular bus that transports cytoplasm proteins to the nucleus – to achieve its ultimate goal, which is the integration into our genes. We can consider it a “stowaway” of the Transportina 3 line ”. Explains Dr. José Alcamí.

According to the researchers of the Institute, this discovery allows us to understand how HIV reaches the cell nucleus and infects us, but it also helps us explain why the mutation in Transportin 3 causes muscle disease in patients since among the proteins it carries there are factors that regulate the expression and processing of muscle proteins.

“We face an exceptional situation, on a common border between rare diseases and infectious diseases, – emphasizes Dr. Alcamí- since the mutant Transportin 3 is involved in two diseases: it causes an inherited muscular dystrophy and protects against infection by the HIV If we can understand the underlying mechanisms, we can design pharmacological and gene therapy strategies to block HIV infection in lymphocytes on the one hand and, on the other, cancel out the action of mutant transportin at the muscular level and thus improve disease symptoms. ”

In the Carlos III Institute and in the rest of the research groups, they are already testing possible therapeutic targets that from the Conquistando Escalones Association are confident that they will come to fruition. The association greatly appreciates the work done as well as all the efforts so that it was published in a magazine of international prestige like the one in question, which is expected to serve as a push to join forces and economic support to achieve the goal , given that despite the efforts and constant struggle carried out since the association, the costs are high and the disease is making the affected people worse, several of them having died in recent years.

The article published in PLOS PATHOGENS can be read in this link: