Viral Components Trafficking with(in) Extracellular Vesicles

Abstract

The global public health burden exerted by viruses partially stems from viruses’ ability to subdue host cells into creating an environment that promotes their multiplication (i.e., pro-viral). It has been discovered that viruses alter cell physiology by transferring viral material through extracellular vesicles (EVs), which serve as vehicles for intercellular communication. Here, we aim to provide a conceptual framework of all possible EV-virus associations and their resulting functions in infection output. First, we describe the different viral materials potentially associated with EVs by reporting that EVs can harbor entire virions, viral proteins and viral nucleic acids. We also delineate the different mechanisms underlying the internalization of these viral components into EVs. Second, we describe the potential fate of EV-associated viral material cargo by detailing how EV can circulate and target a naive cell once secreted. Finally, we itemize the different pro-viral strategies resulting from EV associations as the Trojan horse strategy, an alternative mode of viral transmission, an expansion of viral cellular tropism, a pre-emptive alteration of host cell physiology and an immunity decoy. With this conceptual overview, we aim to stimulate research on EV-virus interactions.

Sphingomyelins in mosquito saliva modify the host lipidome to enhance transmission of flaviviruses by promoting viral protein levels

“…DENV envelop contains lipids, which composition partially varies when viruses derive from mosquito or mammalian cells 57,58 . To evaluate the impact of DENV-lipids on DENV infection, we produced DENV in mosquito and monkey cells, and isolated virions from EVs 59 using discontinuous sucrose density gradient. The purified DENV samples were obtained from our previously-published study, which reported an absence of EV markers (i.e., Alix) in the DENV density fraction 58 , suggesting at least partial separation of DENV from Alix-containing EVs.…”

“…However, infection was similarly enhanced when cells were supplemented with lipids from mock-infected mosquito cell supernatant. Since EVs and DENV have partially overlapping density 59,60 , the mock-infected fraction probably contained EVs, which did not possess or had undetectable amount of the EV marker 58 and the increased infection upon supplementation with mock-infected lipids was likely caused by residual mosquito EV-lipids. In contrast, supplementation with either DENV or mock-infected lipids from mammalian cells did not alter DENV infection (Figure 1G).…”

Exosome-Mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control and Vaccine Design

“…The hijacking of exosome biogenesis might additionally confer the ability of viruses to target crucial components within exosomes, including their own viral nucleic acids, as well as viral proteins or even complete virions. This was notably shown with the hepatitis B virus (HBV) [ 132 ], and since the role of EVs in infections has been studied, examples of viruses using host exosomes as transport systems for their factors have become widespread and are regularly and recently the subject of comprehensive reviews [ 133 , 134 ]. This ability has led to a Trojan Horse hypothesis that exosomes actively contribute to infectious pathogenesis, helping some viruses to evade immune system recognition and sometimes facilitating viral persistence [ 135 ].…”

Exosome-mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control

“…The hijacking of exosome biogenesis might additionally confer the ability to viruses to target crucial components within exosomes, including their own viral nucleic acids, as well as viral proteins or even complete virions. This was notably shown with the hepatitis B virus (HBV) [136] and since the role of EVs in infections has been studied, examples of viruses using host exosomes as transport systems for their own factors have become widespread and are regularly and recently the subject of comprehensive reviews [137,138]. This ability has led to a Trojan Horse hypothesis that exosomes actively contribute to viral pathogenesis and sometimes facilitate viral persistence [139].…”