Analysis of RSK2 and of elements of its signaling pathway in peripheral blood mononuclear cells infected by Human Immunodeficiency Virus Infection (HIV-1)

• Grant number: 18/24025-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2019
• End date: December 31, 2019
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Luiz Mário Ramos Janini
• Grantee: Gabriela Vasconde dos Santos
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

HIV is the causative agent of AIDS and is responsible for infecting mainly cells of the immune system, with emphasis on TCD4+ lymphocytes. According to UNAIDS, in 2017, 36,9 million people are infected with HIV in the world. Currently, based on previous studies, it is known that HIV-1 is influenced by the epigenetics of the host cell. The study of how the virus and its proteins may be affected by differential methylation or histone modifications, and how this affects the ability of the virus to produce a viable progeny is an important focus of the contemporary research. On the other hand, data from the scientific literature indicates that the virus has the capacity to modulate the epigenetics of the host cell and consequently control its replication and suppress viral restriction. The focus of the current project is on RSK2 protein, a serine-threonine kinase of the Ras/MAPK signaling pathway, this pathway is related to several biological processes, such as phosphorylation of transcription factors and modifications taking place on histone terminal regions. In addition, it should be noted that RSK2 plays an important role in HIV-1 infection, since it activates transcription factors such as CREB, NF-kB also being able to induce histone modifications. Due to this, the present project seeks, through the knock down of RSK2 during infected cell cultures, to provide new information about the interplay between RSK2 and HIV-1 replication and how RSK2 targets may be affected after the knock down of RSK2 in culture. The knocking down of RSK2 may represent a possible therapeutic target that may complement antiretroviral therapy.