Study of modulation of epigenetic factors involved in the early stages of infection by HIV-1 in resting TCD4+ cells

• Grant number: 12/12830-5
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2013
• End date: February 28, 2015
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Luiz Mário Ramos Janini
• Grantee: Luiz Mário Ramos Janini
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Juliana Terzi Maricato

Abstract

Epigenetic mechanisms involve a number of changes in chromatin, such as DNA methylation and histone modifications that together with the chromatin remodeling complexes, nuclear architecture and non-coding RNA define the structure of chromatin and its transcriptional activity that culminates in the alteration of gene expression profile of the cell without changes in DNA sequence. It is believed that viruses and bacteria can manipulate the epigenetic processes in order to influence the immune and inflammatory responses of the host, which may also contribute to the development of diseases such as cancer. The infection of CD4 + T cells by HIV-1 or human T-cell leukemia virus-1 (HTLV-1), results in increased DNA methyltransferase activity of the cell, an important enzyme involved in epigenetic changes cellular. The methylation in the LTR promoter of HIV is closely related to the induction of viral latency, although studies suggest that factors other than methylation are crucial for induction of latency. Preliminary data obtained by our group showed that HIV-1 infects resting TCD4+ cells but the HIV-1 infection does not seem to establish productive infection and at levels that can activate the immune system in these cells. In another study show that our group hours after infection, there is an increase of the global methylation in cells infected activated. The need to identify epigenetic factors involved in virus-host interactions will be valuable for better understanding of the factors that influence the key phases of the cycle of HIV-1 in the resting cell still little studied, more than that, the identification of factors involved in these processes may provide new strategies for the treatment of aids that rather than engage in a late phase of infection (latency), may interfere in the early stages of infection in order to inhibit the entry, reverse transcription and / or viral integration. Thus, this study aims to investigate which epigenetic factors, in addition to methylation, are modulated at the beginning of the HIV-1 in resting TCD4 + cells. (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)

NUNES, JORGE MENESES; FURTADO, MARIA NADIEGE; DE MORAIS NUNES, EDSEL RENATA; ARARIPE SUCUPIRA, MARIA CECILIA; DIAZ, RICARDO SOBHIE; RAMOS JANINI, LUIZ MARIO. Modulation of epigenetic factors during the early stages of HIV-1 infection in CD4(+) T cells in vitro. VIROLOGY, v. 523, p. 41-51, OCT 2018. (12/12830-5, 13/09678-0)