Study on the mechanisms by which HIV-1 antagonizes the antiviral activity of interferon induced transmembrane proteins (IFITMs)

• Grant number: 18/08966-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2018
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Cristina Santos da Costa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

HIV-1 is a lentivirus that infects cell of the immune system expressing the CD4 receptor. During replication, the virus subverts cellular machineries on its favor, leading to the production of thousands of new particles and culminating with the death of producer cells. This effect results in a profound depletion of CD4+ cells levels in the host organism, and consequently to AIDS. One of the first responses of the immune system to HIV infection is the cellular signaling mediated by type I and type II interferon. IFITM1, 2 and 3 are transmembrane proteins upregulated by interferon that exert strong anti-HIV activity, acting via distinct mechanisms to halt infection. Different studies have indicated that the antiviral efficacy of IFITMs is determined by its subcellular localization that, in turn, is regulated by amino acid motifs within their N terminal region with are amendable to posttranslational modifications. It is known that the action of other cell-intrinsic anti-HIV factors is antagonized by viral proteins, allowing the virus to evade immune responses. However, the HIV-1 factors responsible for the virus resistance to IFITMs are still elusive. Despite the great importance of IFITMs as cellular defense factors, very little is known about the mechanisms underlying IFITMs antiviral activities and their counteraction mediated by HIV. Therefore, this project aims to shed light on the mechanisms used by HIV to antagonize the action of IFITM1, 2 and 3, contributing to a better understanding of this important aspect of HIV pathogenesis. (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)

TAVARES, LUCAS A.; DE CARVALHO, V, JULIANNE; COSTA, CRISTINA S.; SILVEIRA, ROBERTA M.; DE CARVALHO, ANDREIA N.; DONADI, EDUARDO A.; DASILVA, LUIS L. P.. Two Functional Variants of AP-1 Complexes Composed of either gamma 2 or gamma 1 Subunits Are Independently Required for Major Histocompatibility Complex Class I Downregulation by HIV-1 Nef. Journal of Virology, v. 94, n. 7, APR 2020. (16/05945-1, 16/18207-9, 15/26667-7, 14/02438-6, 18/08966-5, 18/00297-7)