HIV-1 Nef Changes the Proteome of T Cells Extracellular Vesicles Depleting IFITMs and Other Antiviral Factors

Author(s):Show less -

da Silva-Januario, Mara E. ; da Costa, Cristina S. ; Tavares, Lucas A. ; Oliveira, Ana K. ; Januario, Yunan C. ; de Carvalho, Andreia N. ; Cassiano, Murilo H. A. ; Rodrigues, Roger L. ; Miller, Michael E. ; Palameta, Soledad ; Arns, Clarice W. ; Arruda, Eurico ; Leme, Adriana F. Paes ; daSilva, Luis L. P.

• Document type: Journal article
• Source: MOLECULAR & CELLULAR PROTEOMICS; v. 22, n. 12, p. 17-pg., 2023-12-04.

Abstract

Extracellular vesicles (EVs) are biomolecule carriers for intercellular communication in health and disease. Nef is a HIV virulence factor that is released from cells within EVs and is present in plasma EVs of HIV -1 infected individuals. We performed a quantitative proteomic analysis to fully characterize the Nef-induced changes in protein composition of T cell -derived EVs and identify novel host targets of HIV. Several proteins with well -described roles in infection or not previously associated with HIV pathogenesis were specifically modulated by Nef in EVs. Among the downregulated proteins are the interferon -induced transmembrane 1, 2, and 3 (IFITM1-3) proteins, broadspectrum antiviral factors known to be cell -to -cell transferable by EVs. We demonstrate that Nef depletes IFITM13 from EVs by excluding these proteins from the plasma membrane and lipid rafts, which are sites of EVs biogenesis in T cells. Our data establish Nef as a modulator of EVs' global protein content and as an HIV factor that antagonizes IFITMs. (AU)

• FAPESP's process: 22/15928-8 - Study of the molecular mechanisms used by the HIV-1 Nef protein to neutralize host cell defense strategies
• Grantee: Luis Lamberti Pinto da Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/00297-7 - Study of the effects of HIV-1 Nef on the host-cell endomembrane system and their implications in viral pathogenesis
• Grantee: Luis Lamberti Pinto da Silva
• Support Opportunities: Regular Research Grants