RESUMO
Oropouche fever, a debilitating illness common in South America, is caused by Oropouche virus (OROV), an arbovirus. OROV belongs to the Peribunyaviridae family, a large group of RNA viruses. Little is known about the biology of Peribunyaviridae in host cells, especially assembly and egress processes. Our research reveals that the small GTPase Rab27a mediates intracellular transport of OROV induced compartments and viral release from infected cells. We show that Rab27a interacts with OROV glycoproteins and colocalizes with OROV during late phases of the infection cycle. Moreover, Rab27a activity is required for OROV trafficking to the cell periphery and efficient release of infectious particles. Consistently, depleting Rab27a's downstream effector, Myosin Va, or inhibiting actin polymerization also hinders OROV compartments targeting to the cell periphery and infectious viral particle egress. These data indicate that OROV hijacks Rab27a activity for intracellular transport and cell externalization. Understanding these crucial mechanisms of OROV's replication cycle may offer potential targets for therapeutic interventions and aid in controlling the spread of Oropouche fever.
Assuntos
Cadeias Pesadas de Miosina , Miosina Tipo V , Liberação de Vírus , Proteínas rab27 de Ligação ao GTP , Proteínas rab27 de Ligação ao GTP/metabolismo , Humanos , Liberação de Vírus/fisiologia , Miosina Tipo V/metabolismo , Miosina Tipo V/genética , Cadeias Pesadas de Miosina/metabolismo , Infecções por Bunyaviridae/metabolismo , Infecções por Bunyaviridae/virologia , Orthobunyavirus/metabolismo , Orthobunyavirus/fisiologia , Replicação Viral/fisiologia , Animais , Interações Hospedeiro-PatógenoRESUMO
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, broad-spectrum antiviral factors known to be cell-to-cell transferable by EVs. We demonstrate that Nef depletes IFITM1-3 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.
Assuntos
Vesículas Extracelulares , Infecções por HIV , HIV-1 , Humanos , Linfócitos T , Proteoma/metabolismo , Proteômica , Vesículas Extracelulares/metabolismo , Interferons/metabolismo , Infecções por HIV/metabolismo , Antivirais/metabolismoRESUMO
Recent seroprevalence studies in animals detected Rocio virus in regions of Brazil, indicating risk for re-emergence of this pathogen. We identified Rocio virus RNA in samples from 2 human patients for whom dengue fever was clinically suspected but ruled out by laboratory findings. Testing for infrequent flavivirus infections should expedite diagnoses.