Expression of antiviral factors and endogenous retroviruses in HIV-1 infected mothers and newborns

• Grant number: 12/18837-1
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2013
• End date: February 28, 2015
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Maria Notomi Sato
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The maternal-fetal interface is the main site of immunoregulation during pregnancy, mediated by cell and factors necessary for the maintenance and development of the semi-allogeneic fetus. In the presence of a chronic infection such as HIV, these tolerance mechanisms must develop a crucial role in protecting the fetus and neonate, since a large proportion of infants (65-80%) born to mothers infected with HIV, that even in the absence of treatment, does not acquire the infection (CDC 2007). The investigation of the mother-RN in HIV infection is an important opportunity to evaluate the immunological mechanisms, especially those related to innate immunity. The proposed project is to evaluate the innate immune response of infected mothers and their HIV-1 neonates, the expression of antiviral factors and examine the potential modulatory agonists of Toll-like receptors. Also assess the influence of the expression of endogenous retroviruses (HERV-K) in the expression of antiviral factors. To this end, we will analyze the transcriptional expression of antiviral factors (APOBEC3F and 3G, TRIM-5alpha, TRIM22, defensin-alpha1, teterina, MxA, IFN-beta) and viral factors, HIV Gag and Gag of HERV-K in cells mononuclear (CMN) from peripheral blood of the mother, umbilical cord and placental tissue. It will also evaluate the protein expression of antiviral factors (APOBEC3F and 3G, TRIM-5alpha) and viruses (HIV and HERV-K). The potential modulatory agonists of Toll-like receptors in the expression of antiviral factors, will be analyzed in CMN stimulated by agonists of TLR3, TLR7 and TLR7 / 8 by protein and mRNA expression of antiviral factors and viral Gag region (HIV and HERV- K) and the production of chemokines / cytokines. The frequency of CD4 + and CD8 + naïve cells, central memory and peripheral expressing APOBEC3G and IFN-gamma, TNF-alpha, MIP-1alpha will be evaluated after stimulation with agonists of TLR7 / 8, HERV-K and p24 of HIV-1. The understanding of the innate immune response, with emphasis on antiviral factors and endogenous retroviruses and their modulation by ligands for TLRs, can promote possible correlates of protection and provide grants to develop new formulations of HIV vaccines. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA, NATALLI ZANETE; CARDOSO, ELAINE CRISTINA; DA SILVA OLIVEIRA, LUANDA MARA; DE LIMA, JOSENILSON FEITOSA; CALVIELLI CASTELO BRANCO, ANNA CLAUDIA; DE SOUZA AVEIRO RUOCCO, ROSA MARIA; ZUGAIB, MARCELO; DE OLIVEIRA FILHO, JOAO BOSCO; DA SILVA DUARTE, ALBERTO JOSE; SATO, MARIA NOTOMI. Upregulation of Innate Antiviral Restricting Factor Expression in the Cord Blood and Decidual Tissue of HIV-Infected Mothers. PLoS One, v. 8, n. 12, DEC 18 2013. (12/18837-1)

PEREIRA, NATALLI ZANETE; BRANCO, ANNA CLAUDIA CALVIELLI CASTELO; MANFRERE, KELLY CRISTINA GOMES; DE LIMA, JOSENILSON FEITOSA; YOSHIKAWA, FABIO SEITI YAMADA; MILANEZ, HELAINE MARIA BESTETI PIRES MAYER; PEREIRA, NAIURA VIEIRA; SOTTO, MIRIAM NACAGAMI; DUARTE, ALBERTO JOSE DA SILVA; SATO, MARIA NOTOMI. Increased Expression on Innate Immune Factors in Placentas From HIV-Infected Mothers Concurs With Dampened Systemic Immune Activation. FRONTIERS IN IMMUNOLOGY, v. 11, AUG 25 2020. (12/21364-8, 12/18837-1)