In her PhD thesis, Helena Crespo-Otano has studied the mechanism of the action of the small ruminant lentivirus (SRLV), a type of virus in the same family as HIV and which infects sheep and goat species. Lentiviruses are viruses responsible for slow infections that damage the immune system and which cause a range of clinical symptoms (nervous, pulmonary, arthritic and mammary). The thesis is entitled “Papel del receptor de la manosa y de la polarización de macrófagos en la infección por lentivirus de pequeños rumiantes” [Role of the mannose receptor and the polarization of macrophages due to lentivirus infection in small ruminants].
In her work, she identified and characterised the ovine mannose receptor (MR), a cell receptor involved in the infectious process when the virus is allowed to penetrate the cells of the animals. The target cells of these lentiviruses are the macrophages. These cells are capable of modifying their genetic expression depending on the external stimuli they are exposed to (which is known as polarisation), so that they can adapt their function to the one-off needs of the organism and are, therefore, a key component in the development of a beneficial immune response for the individual.
As Helena Crespo explained, “what is observed in the flocks infected by the small ruminant lentivirus is a fall in productivity, an increase in mortality caused by secondary infections, and premature culling (the livestock are separated from the flock) of the infected animals, which leads to an increase in the restocking rate in the flock and considerable economic losses”.
Right now, there are no effective vaccines or treatments to combat infections of this type, so innate immunity factors are being studied as an effective alternative to treat or prevent these infections. "The cells of the immune system, like the macrophages, have mechanisms to counteract the infection. For example, in their membranes they have so-called pathogen pattern recognition receptors, which enable them to recognise and neutralise them,” pointed out the researcher. Specifically, the so-called MR (mannose receptor) could be a “safe” door of entry for certain bacteria, protozoa, parasites and viruses like SRLVs into the target cell, which would encourage infection and the development of associated pathologies.
In this context, the thesis deals in depth with hitherto unknown aspects of infection by small ruminant leniviruses.“We have identified and characterised the ovine MR gene and have determined its involvement in the entry of the virus into the cells that express it”. The author of the work studied the role played by this molecule in the development of various pathologies associated with infection. So “after analysing the MR expression in 124 tissue samples from 31 animals, we saw that there was a greater expression of the mannose receptor in the more affected organs". Firstly, the existence of differentiated populations of macrophages was demonstrated in sheep and goats, the so-called M1 (proinflammatory) and M2 (anti-inflammatory), which have opposite restrictive capacities over lentiviruses. Furthermore, it was observed that the infection induces M2 polarisation, which favours the establishing and evolution of the disease, opening up the possibility of identifying new therapeutic targets to combat lentiviral infections.
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