ESCRT machinery components are required for Orthobunyavirus particle production in Golgi compartments

Author(s):Show less -

Barbosa, Natalia S. ^[1] ; Mendonca, Leila R. ^{[1, 2]} ; Dias, Marcos V. S. ^{[1, 3]} ; Pontelli, Marjorie C. ^[1] ; da Silva, Elaine Z. M. ^[3] ; Criado, Miria F. ^[1] ; da Silva-Januario, Mara E. ^[1] ; Schindler, Michael ^[4] ; Jamur, Maria C. ^[3] ; Oliver, Constance ^[3] ; Arruda, Eurico ^{[1, 3]} ; daSilva, Luis L. P. ^{[1, 3]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Virus Res, Ribeirao Preto, SP - Brazil

^[2] Oswaldo Cruz Fdn FIOCRUZ, Dept Virol & Expt Therapy LAVITE, IAM, Recife, PE - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, Ribeirao Preto, SP - Brazil

^[4] Univ Hosp Tubingen, Mol Virol Human Infect Dis, Inst Med Virol & Epidemiol, Tubingen - Germany

• Document type: Journal article
• Source: PLOS PATHOGENS; v. 14, n. 5 MAY 2018.
• Web of Science Citations: 3

Abstract

Peribunyaviridae is a large family of RNA viruses with several members that cause mild to severe diseases in humans and livestock. Despite their importance in public heath very little is known about the host cell factors hijacked by these viruses to support assembly and cell egress. Here we show that assembly of Oropouche virus, a member of the genus Orthobunyavirus that causes a frequent arboviral infection in South America countries, involves budding of virus particles toward the lumen of Golgi cisternae. As viral replication progresses, these Golgi subcompartments become enlarged and physically separated from Golgi stacks, forming Oropouche viral factory (Vfs) units. At the ultrastructural level, these virally modified Golgi cisternae acquire an MVB appearance, and while they lack typical early and late endosome markers, they become enriched in endosomal complex required for transport (ESCRT) proteins that are involved in MVB biogenesis. Further microscopy and viral replication analysis showed that functional ESCRT machinery is required for efficient Vf morphogenesis and production of infectious OROV particles. Taken together, our results indicate that OROV attracts ESCRT machinery components to Golgi cisternae to mediate membrane remodeling events required for viral assembly and budding at these compartments. This represents an unprecedented mechanism of how viruses hijack host cell components for coordinated morphogenesis. (AU)

• FAPESP's process: 09/54014-7 - Acquisition of a biophotonic imaging system and a multiphoton microscopy system for in vivo imaging
• Grantee: Enilza Maria Espreafico
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/02438-6 - Studies with Bunyaviridae that produce human disease
• Grantee: Luiz Tadeu Moraes Figueiredo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/25812-0 - Study on the molecular interactions of HIV-1 with the endomembrane system of the host cells
• Grantee: Luis Lamberti Pinto da Silva
• Support Opportunities: Regular Research Grants