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18/10/2019

Vall d'Hebron identifies a new cell type as the main target and reservoir in the tissues of people infected with HIV

TRM_VIH

18/10/2019

Memory-resident cells (TRM) are one of the largest reservoirs of HIV, since they are the most abundant cells in peripheral tissues.

A study led by Dres. Meritxell Genescà and María José Buzón, leading investigators of the Vall d'Hebron Research Institute's http://www.vhir.org/portal1/grup-equip.asp?t=malalties-infeccioses&s=recerca&contentid=186953 Infectious Diseases Research Group (VHIR), have discovered that resident memory cells (TRMs) can be one of the Higher reserves of HIV, as they are the most abundant cells in peripheral tissues, such as skin or gastrointestinal tract, as well as those present in adipose tissue, lymph tissue or even organs. The TRM play a double role: on the one hand, they are the main target for the HIV virus and, on the other, represent a viral reservoir in tissues such as the cervix. The study, in which the Germans Trias i Pujol University Hospital, the Hospital del Mar, the Germans Trias i Pujol Research Institute and the IrsiCaixa AIDS Research Institute also collaborate, is published in the journal Nature Communications. One of the main obstacles to the eradication of the HIV virus is the reservoirs that store the virus in a state of latency, or with low levels of replication, while the patients are in antiretroviral treatment. These reservoirs can be established in different cells and tissues throughout the body. The characteristics of the reservoirs and the viruses that emerge when the treatment is interrupted suggest that the reservoirs are established in different tissues few days after becoming infected, including the mucous membranes where the virus is transmitted. Once we deepen in the study of the reservoir, we know that long-life cells can be good candidates to shelter the virus latently because of their capacity for homeostatic proliferation, that is, physiologically proliferating themselves The same to keep the memory of the immune response. Memory resident cells are important here. The TRMs are located in peripheral tissues, such as the female genital tract and, having low migration capacity, we can not find them in blood. These cells are prepared to respond very quickly to tissues exposed to pathogens and are characterized by long longevity and a capacity for self-renewal, which makes them excellent candidates for reservoir. The objective of the study was to verify whether the TRM could be a reservoir of HIV, which would make them one of the largest reservoirs of the virus, since they are the most abundant cells in tissues. In general, studies are carried out preferably in the blood because it is the most accessible sample, but "in the bloodstream we only find 2% of CD4 + T lymphocytes that are the main target of the HIV virus. Therefore, the large volume of CD4 + T is in the tissues and that is where we have to look for the reservoirs, "says Dr. Meritxell Genescà. "On the other hand we also wanted to deepen the study of the cervical tissue as a possible reservoir, since the first infectious tissues would be very relevant in view of the establishment of the reservoir, and women are poorly represented in these types of studies ", adds the Dra. Genescà. Using ex vivo infected cervical explants, the research group came to the conclusion that memory-resident cells represent a preferential target for the virus. They also compared cervical tissue of healthy women with women with antiretroviral treatment. And, despite the antiretroviral treatment, which achieves viral suppression in the blood, the tissues can still detect alterations, In fact, the levels of TRM activation in HIV + women are different from healthy women. On the other hand, they also measured the amount of detectable virus for both DNA and RNA. Thus, they concluded that "in the tissues of the cervical mucosa there is a significantly higher level of virus remaining than in the blood and that the majority of the cells that contain this virus are TRM", affirms the Dra. Mailbox The first signatories of this article are predoctoral students Jon Cantero and Judith Grau, who emphasize the fact that one of the characteristics of the TRM is the expression of the CD69 marker. "A path is opened for better identification of HIV reservoirs in tissues and it is through the CD69 marker, which behaves differently in blood than in tissues," they declare. In blood, CD69 means a state of cellular activation and, for this reason, so far it was not studied since in the reservoirs what is sought are cells in a state of rest. Instead, in tissues, CD69 becomes a residence marker, that is, that the cells remain in tissues. "Therefore, new therapies aimed at the elimination of the virus that persists in these patients must take into account this cell type, present in all tissues," concludes Dr. Genescà. In the study, the Gynecology service of Vall d'Hebron University Hospital, where patients are visited routinely for the control of cervical disease, is very important. Within this service, we must emphasize the participation of Dr. Cristina Centeno, who has actively contributed to the recruitment of the participants. And, of course, we must thank the voluntary participation of the patients. This study has received funding from the Ministry of Economy and Competitiveness-Carlos III Health Institute, the Strategic Research and Innovation Plan for Health (PERIS) of the Generalitat de Catalunya and the Dexeus Salud Salud de la Mujer Foundation, which year Past he awarded a scholarship to Dr. Genescà in the area of Basic Research in Obstetrics and Gynecology.

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