Role of myosins in dendritic cell mediated trans-infection of HIV-1 and in HIV-1 replication in macrophages

• Grant number: 14/23225-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: February 01, 2016
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Bruna Cunha Gondim de Alencar
• Grantee: Bruna Cunha Gondim de Alencar
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/01733-8 - Siglec1 interactome after HIV-1 binding, BP.MS; 17/01313-3 - Validating siRNA silence and specificity for myosin expressed in macrophages, BP.IC; 16/11679-2 - Involvement of myosins in Dendritic cell-mediated trans-infection of HIV-1, BP.MS

Abstract

HIV-1 debilitates the immune system especially due to its ability to infect CD4+ T lymphocytes. However, other cells of the immune system also interact with the virus and are important in the course of infection. That is the case of macrophages and dendritic cells. Macrophages can be directly infected by HIV-1, are involved in AIDS-associated dementia, and are considered viral reservoirs. Dendritic cells, on the other hand, are capable of transmitting the virus to target CD4+ T cells even without being directly infected, through a mechanism known as trans-infection. For that reason, dendritic cells are thought to be important for HIV-1 dissemination. Myosins are motor proteins that travel on the actin network and mediate many of its functions. Considerable evidence points to the fact that HIV-1 uses the actin network at several steps of its cycle. Despite that, little is known about the motor proteins involved in HIV-1 replication and transmission. The goal of this project is to study the role of myosins in HIV-1 infection of macrophages and in dendritic cell-mediated trans-infection. The project aims at describing the myosins that participate in these processes and their role, by silencing myosin expression using RNAi technology in primary human cells. The description of new host proteins involved in HIV-1 cycle can pave the way for the development of new treatments directed at eliminating viral reservoirs and restricting HIV-1 transmission. (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)

DE LIMA, DHEMERSON SOUZA; NUNES, VINICIUS C. L.; OGUSKU, MAURICIO M.; SADAHIRO, AYA; PONTILLO, ALESSANDRA; ALENCAR, BRUNA DE CUNHA. Polymorphisms in SIGLEC1 contribute to susceptibility to pulmonary active tuberculosis possibly through the modulation of IL-1 beta. INFECTION GENETICS AND EVOLUTION, v. 55, p. 313-317, NOV 2017. (15/23395-6, 13/06142-1, 14/23225-0)

DOS REIS, EDIONE CRISTINA; CORDEIRO LEAL, VINICIUS NUNES; DA SILVA SOARES, JAINE LIMA; FERNANDES, FERNANDA PEREIRA; DE LIMA, DHEMERSON SOUZA; DE ALENCAR, BRUNA CUNHA; PONTILLO, ALESSANDRA. Flagellin/NLRC4 Pathway Rescues NLRP3-Inflammasome Defect in Dendritic Cells From HIV-Infected Patients: Perspective for New Adjuvant in Immunocompromised Individuals. FRONTIERS IN IMMUNOLOGY, v. 10, JUN 11 2019. (15/23395-6, 18/04361-1, 15/17373-0, 14/23225-0, 17/10824-1)

MATOZO, TAIS; KOGACHI, LETICIA; DE ALENCAR, BRUNA CUNHA. Myosin motors on the pathway of viral infections. CYTOSKELETON, v. 79, n. 6-8, p. 23-pg., 2022-07-22. (14/23225-0)