Study of the mechanism of Orthobunyavirus intracelular transport and externalization

• Grant number: 20/11900-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2021
• End date: June 23, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Juan Oswaldo Concha Casaverde
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 23/03946-4 - Temporal proteomic analysis of OROV infection reveals manipulation of wide range of host proteins, BE.EP.DR

Abstract

The Oropouche Virus (OROV) is an enveloped virus in the family Peribunyaviridae and the genus Orthobunyavirus. Its genome consists of three single-stranded RNA segments with negative polarity, which encode for its four structural proteins: two surface glycoproteins (Gn and Gc), and two internal proteins (the polymerase and the nucleocapsid protein); and for two non-structural proteins (NSm and NSs). OROV is the etiological agent of Oropouche fever, one of the most frequent viral febrile diseases in Brazil, and which, due to the common clinical symptoms with other viral febrile diseases, and difficulties in diagnosis, presents a distribution and number of cases still underestimated. There is no vaccine available for OROV and Oropouche fever is considered a candidate for the next epidemic in the Americas. However, despite the large number of cases and their importance in public health, little is known about the cell biology of OROV and Orthobunyavirus in general, and the little that is known is derived from studies with the Bunyawera Virus (BUNV) , which causes a disease without much relevance. One of the least understood aspects about the replicative cycle of Orthobunyaviruses is the assembly and externalization processes, the latter being addressed in the present study. Due to the fact that the budding process of Orthobunyaviruses has characteristics similar to that of Intraluminal Vesicles (ILVs) in Multivesicular Bodies (MVBs), it was hypothesized that OROV could also be externalized in a similar way to ILVs. In fact, preliminary results show the involvement of Rab27A and Rab27B proteins (which control the externalization of ILVs) in the externalization of OROV. Based on this hypothesis, the objective of the present work is to clarify and propose a mechanism for the OROV transport and externalization process, using this virus as a model for understanding the general cellular mechanisms of Orthobunyaviruses. (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)

CONCHA, JUAN O.; GUTIERREZ, KRISTEL; BARBOSA, NATALIA; RODRIGUES, ROGER L.; DE CARVALHO, ANDREIA N.; TAVARES, LUCAS A.; RUDD, JARED S.; COSTA, CRISTINA S.; ANDRADE, BARBARA Y. G.; ESPREAFICO, ENILZA M.; et al. Rab27a GTPase and its effector Myosin Va are host factors required for efficient Oropouche virus cell egress. PLOS PATHOGENS, v. 20, n. 8, p. 24-pg., 2024-08-01. (19/26119-0, 19/02945-9, 23/02880-0, 22/04533-2, 20/11900-6, 21/01182-1, 16/18356-4, 18/00297-7, 19/27725-1, 19/02418-9)

ALVIM, JONAS C.; BOLT, ROBERT M.; AN, JING; KAMISUGI, YASUKO; CUMING, ANDREW; SILVA-ALVIM, FERNANDA A. L.; CONCHA, JUAN O.; DA SILVA, LUIS L. P.; HU, MEIYI; HIRSZ, DOMINIQUE; et al. The K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper. NATURE COMMUNICATIONS, v. 14, n. 1, p. 16-pg., 2023-03-23. (20/11900-6, 19/26119-0, 19/02418-9)