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Maternal-fetal interaction, antiviral factors and endogenous retroviruses in HIV-1 infection

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Natalli Zanete Pereira
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Maria Notomi Sato; Niels Olsen Saraiva Câmara; Patricia Palmeira Daenekas Jorge; Maria Isabel de Moraes Pinto; Camila Malta Romano
Advisor: Maria Notomi Sato

Innate immunity at the maternal-fetal interface is one of the main protection mechanisms in the antiviral response, especially in HIV-1 infection. In this work, we present the influence of maternal HIV-1 infection on the expression of antiviral factors, inflammasome molecular complex and human endogenous retroviruses (HERV), in maternal mononuclear cells (MNCs), umbilical cord cells (newborns, NB), colostrum and placental tissue. The results show that in infected mothers cells has an increase in mRNA expression of antiviral factors, such as IFN type I and III, DAMPs (damage-associated molecular patterns) and HERVs. However, in protein analysis, these differences are not confirmed, indicating that the immune system is able to detect the virus, or even the damage caused by the infection, but controls the exacerbated protein production. Under stimulation of the TLR (Toll-like receptor) agonist, CMNs do not change among the RNs. In addition, by evaluating the levels of &#223-chemokines, CCL5 and CCL3, and of IFN-&#945 in the supernatants of CMNs cultures, LPS activation was able to decrease the production of CCL3 and CCL5 in CMNs of HIV-infected mothers compared to control mothers, nevertheless CL097 promoted similar levels between HIV-infected mothers and control group. In RNs, while CCL5 levels are lower than in adults, CCL3 levels are similar. TLR7/8 agonist was able to restore IFN- secretion in the HIV-infected group. In contrast, the TLR7/8 agonist was able to restore IFN- secretion in HIV-infected group. In addition, in placental villi, there is intense modification in the mRNA expression of the analyzed factors, whether they are antiviral, such as IFN type I (IFN-&#945), type III (IFN-&#955), related to cell damage (DAMPs and their receptors). Among DAMPs, increased expression of S100A9 and HMGB1 and their receptors RAGE, TLR4 and TLR9 was observed in placental villi of HIV-infected mothers, however, serum HMGB1 levels are decreased in infected-mothers and exposed-newborns. About the cytokines serum levels, reduced levels of HMGB1, IL-6 and IL-1&#223 were observed in the exposed-NBs, which evidences an inflammatory status control in HIV-1 exposure. We also observed the presence of free HERV-W or exosomes levels in serum in both groups analyzed. In colostrum, we did not find differences in inflammatory factors and HERVs analysis indicating that, in this compartment, the infection does not alter the expression patterns of these targets. The effectiveness of antiviral status and suppression of the inflammatory environment can balance the placental immune response, promoting homeostasis for fetal development and protection of HIV-1 infection in neonates. (AU)

FAPESP's process: 12/21364-8 - Expression of antiviral factors and endogenous retroviruses constitutive and induced by agonists of toll-like receptors in HIV-1 infected mothers and newborns
Grantee:Nátalli Zanete Pereira
Support Opportunities: Scholarships in Brazil - Doctorate