The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell–Cell Communication: New Insights on Virus–Host Interactions

Abstract

The arthropod-borne flaviviruses are important human pathogens, and a deeper understanding of the virus–host cell interaction is required to identify cellular targets that can be used as therapeutic candidates. It is well reported that the flaviviruses hijack several cellular functions, such as exosome-mediated cell communication during infection, which is modulated by the delivery of the exosomal cargo of pro- or antiviral molecules to the receiving host cells. Therefore, to study the role of exosomes during flavivirus infections is essential, not only to understand its relevance in virus–host interaction, but also to identify molecular factors that may contribute to the development of new strategies to block these viral infections. This review explores the implications of exosomes in flavivirus dissemination and transmission from the vector to human host cells, as well as their involvement in the host immune response. The hypothesis about exosomes as a transplacental infection route of ZIKV and the paradox effect or the dual role of exosomes released during flavivirus infection are also discussed here. Although several studies have been performed in order to identify and characterize cellular and viral molecules released in exosomes, it is not clear how all of these components participate in viral pathogenesis. Further studies will determine the balance between protective and harmful exosomes secreted by flavivirus infected cells, the characteristics and components that distinguish them both, and how they could be a factor that determines the infection outcome.

Double-Stranded RNA Viruses Are Released From Trichomonas vaginalis Inside Small Extracellular Vesicles and Modulate the Exosomal Cargo

“…For example, the presence of viral RNA and proteins was reported in exosomes secreted by Rift Valley Fever Virus (RVFV) infected cells, although they do not serve for the virus transmission ( Ahsan et al, 2016 ), while viruses such as hepatitis C virus (HCV), and porcine reproductive and respiratory syndrome virus (PRRSV) can infect naive cells via naked viral RNA within exosomes ( Longatti et al, 2015 ; Wang et al, 2018 ). Other viruses include human polyomavirus 2, ( Morris-Love et al, 2019 ), Dengue virus ( Reyes-Ruiz et al, 2020 ), Rotavirus ( Iša et al, 2020 ), and Norovirus ( Todd and Tripp, 2020 ) exploit exosomes for transmission of the whole virions. Thus, we initially addressed the question of whether and if so, which viral components are present in sEVs derived from T. vaginalis that harbor TVV1, TVV2, and TVV3.…”

Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry

“…RAB7A interacts with the SARS-CoV-2 NSP7 protein (73), a viral protein required for the RdRP complex assembly (74). Since the RAB7A is required for exosome secretion (75), SARS-CoV-2 could use an exosome pathway as a route of entry or egress, similar to other viruses (76). Exosomes isolated from COVID-19 patients contain the SARS-CoV-2 RNA and proteins implicated in the exosomal cargo (77).…”

Protein-Driven Mechanism of Multiorgan Damage in COVID-19

“…The role of EV in SARS-CoV-2 infection has been reviewed recently by Hassanpour et al [ 56 ] on the basis of their contribution to spread the virus, based on their role in transporting receptors as CD9 and ACE2, which make recipient cells susceptible to virus docking. It is also worth mentioning that EVs play important roles in the viral spread and replication [ 57 , 58 ], particularly of HIV, HCV and SARS [ 59 ], Newcastle disease virus [ 60 ], HPV [ 61 ], flavivirus infection [ 62 ], as well as in the pathogenicity of certain viruses in the nervous system [ 63 ].…”