HIV induces epigenetic changes and these are not reversed with treatment
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Changes in genome methylation are associated with various types of HIV infection progression.
It's not just genes that determine who we are. Our environment has a lot to say and, in fact, can influence our genome. Of all the changes caused by the environment, there are some that generate mutations, since they modify the sequence of the genetic code —the "alphabet" used by the DNA and which defines us as we are— but there are others that do not. The latter are known as epigenetic changes and, although they do not alter this code, they do affect the way genes are expressed. One of the epigenetic mechanisms is carried out through the chemical modification (methylation) of certain components of the DNA, causing genes to be activated or inactivated to produce proteins, like a switch. It is these variations that, among others, generate differences between people; differences that may be key to understanding some diseases.
Based on this approach and related to another IrsiCaixa project, the research group led by IrsiCaixa researcher Javier Martínez-Picado has recently published a study in the Clinical Infectious Diseases journal which confirms that some epigenetic changes —specifically the methylation of certain regions of the genome— can influence the progression of HIV infection in the absence of treatment. This methylation would be altering the expression of some genes related to the immune response. "Not only have we proven that the virus can modify the methylation of an individual's genome, but when we compare people before and after receiving antiretroviral treatment, we see that the treatment does not reverse these changes", says Martínez-Picado.
The team analysed and compared the methylation profile of the cells that attack the HIV, immune system cells known as CD4+ T cells, in a total of 85 people. These included people with HIV, elite controllers —people with HIV who are able to maintain an undetectable viral load in the blood in the absence of treatment— and HIV-negative individuals. Thus, they have been able to observe that there are differences in the DNA methylation profiles of these groups of individuals, who are at different stages of infection and control quite differently the virus.
Thus, the study confirms that the methylation of the genome varies according to the status and progression of HIV infection and that, therefore, these variations can influence the control of the infection in the absence of treatment.