This is a first, as underlined by the National Agency for Research on AIDS and Viral Hepatitis (ANRS) (June 17): a research team has highlighted “a sex-dependent genetic mechanism in the innate immune response which takes place during the acute phase of HIV-1 infection ”. In other words: men and women are not equal in the first stage of HIV-1 infection. Explanations.
As an agency press release explains, the results of this work, supported by the ANRS and published on June 18 in the journal JCI Insight, shed new light on the “differences in viral load between men” and women in the early stage of HIV-1 infection. ” If these differences had already been observed previously, this work, led by Jean-Charles Guéry, in collaboration with Laurence Meyer, Pierre Delobel and Michaela Müller-Trutwin (1), contributes to a better understanding of the mechanisms of HIV infection -1. In order to understand the differences in viral load observed in the acute phase of HIV infection in women and men, the researchers focused on central cells in the innate immune response to infection. viral: plasmacytoid dendritic cells. The latter have receptors called “TLR7”, explains the ANRS press release.
When viral RNA binds to this receptor, plasmacytoid dendritic cells then secrete large quantities of molecules, such as type I interferon (IFN-I). IFN-I has both antiviral activity and properties that regulate the immune response. The gene coding for the TLR7 receptor is located on chromosome X. This chromosome is possessed in two copies by women (XX) and only one in men (XY). In women, in order not to overexpress the genes of the X chromosome, a mechanism inactivates the genes carried by one of the two chromosomes. However, the same team showed in 2018 that the gene coding for the TLR7 receptor escaped this inactivation. Thus, the receptor is present in significantly greater quantity in women than in men. In their work, the authors studied a frequent variant of the gene coding for the TLR7 receptor, the “T” allele. Between 30 and 50% of European women carry at least one T allele. The presence of this allele decreases the quantity of the TLR7 receptor and the production of IFN-I by plasmacytoid dendritic cells in women, but not in men. By comparing the clinical parameters of patients in the French ANRS CO6 Primo cohort of people infected with HIV-1 in the acute phase, the researchers observed that women who carry the T allele in two copies (homozygotes) also have fewer symptoms of acute HIV-1 infection and see a significant reduction in their viral load compared to women without the T allele.
What do scientists conclude from this? That “TLR7 is a key effector molecule which, when overexpressed, exerts a deleterious effect on viral load in acute HIV-1 infection”. These results are “unexpected, because they suggest that IFN-I, less secreted in the carriers of the T allele of the gene coding for TLR7, is not responsible for the better control of the viral load, as many hypotheses suggest. have suggested so far, ”recalls the ANRS. “This molecule would even play a deleterious role in the acute phase of the infection if its levels are too high. From now on, studies of immune mechanisms, as well as strategies aimed at reducing viral reservoirs using molecules capable of specifically binding to the TLR7 receptor, will have to take this discovery into account ”, conclude the researchers.
(1): Jean-Charles Guéry (Center for Physiopathology of Toulouse Purpan, University of Toulouse III-Paul Sabatier, Inserm, CNRS), in collaboration with Laurence Meyer (Center for Research in Epidemiology and Population Health, Inserm, University of Paris- Saclay), Pierre Delobel (Department of Infectious and Tropical Diseases, Toulouse University Hospital, Inserm) and Michaela Müller-Trutwin (HIV, inflammation and persistence unit, Institut Pasteur).
ANRS CO6 Primo cohort Initiated in 1996, the ANRS CO6 Primo cohort has so far included 2,426 patients living with HIV-1 for less than three months. Its main objective is to improve the pathophysiological knowledge on primary HIV infection. It now makes it possible to provide information on the impact of early treatment after primary infection, transient or prolonged, compared to deferred treatment on the long-term prognosis; are thus studied markers of inflammation and decline in viral reservoirs.
SOURCE: https://www.w24news.com
