Characterization of two new proteins (LOC339779 e C1QBP) downregulated by Nef of HIV-1 in lymphocytes CD4+

• Grant number: 11/22522-3
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2012
• Effective date (End): January 31, 2013
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal researcher: Rodrigo Orlandini de Castro
• Grantee: Mara Elisama da Silva Januário
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The HIV-1 (human immunodeficiency virus type 1), targets CD4+ T lymphocytes and this leads to severe reduction in the number of T cells CD4+, resulting to the collapse of the immune system and progression of acquired immunodeficiency syndrome (AIDS). The successful replication of HIV-1 depends on its accessory proteins; among them is Nef. The product of nef gene represents the main transcript from HIV-1 found in the early stages of infection and this has a critical step to the success of viral infection. Nef interacts with members of the intracellular traffic proteins machinery, creating an environment satisfactory for viral replication, being able to negatively regulate cell surface proteins which play important roles in immune responses, such as CD4 and molecules of the Major Histocompatibility Complex type I (MHC-I). This is due to the ability of Nef to alter the routes of intracellular traffic of proteins, accelerating the endocytosis and degradation of CD4 from the plasma membrane and blocking the transport of MHC-I to the cell surface. Thus, Nef protein is directly associated with modifications on plasma membrane protein expression of infected cells. Some receptors such as CD80, the CD86, CD28, CCR5 and CXCR4 also have their expression affected on the plasma membrane by Nef. Experiments carried out by our research group allowed us to identify two new proteins, LOC339779 and C1QBP, whose expression was reduced by HIV-1 Nef in T cells CD4+. Therefore, this project proposes to characterize the effect of Nef in downrregulating these proteins. This project will greatly contribute to better understanding the action of Nef on intracellular protein traffic and the interference of C1QBP e LOC339779 on the viral pathogenesis.