The Role of Extracellular Vesicles as Allies of HIV, HCV and SARS Viruses

Abstract

Extracellular vesicles (EVs) are lipid bilayer-enclosed entities containing proteins and nucleic acids that mediate intercellular communication, in both physiological and pathological conditions. EVs resemble enveloped viruses in both structural and functional aspects. In full analogy with viral biogenesis, some of these vesicles are generated inside cells and, once released into the extracellular milieu, are called “exosomes”. Others bud from the plasma membrane and are generally referred to as “microvesicles”. In this review, we will discuss the state of the art of the current studies on the relationship between EVs and viruses and their involvement in three important viral infections caused by HIV, HCV and Severe Acute Respiratory Syndrome (SARS) viruses. HIV and HCV are two well-known pathogens that hijack EVs content and release to create a suitable environment for viral infection. SARS viruses are a new entry in the world of EVs studies, but are equally important in this historical framework. A thorough knowledge of the involvement of the EVs in viral infections could be helpful for the development of new therapeutic strategies to counteract different pathogens.

COVID-19 and Extracellular Vesicles: An Intriguing Interplay

“…During cellular infection, some viruses may use this machinery by packing viral proteins and RNA into vesicles that are later released to the extracellular space, thereby contributing to the spread of the virus to non-infected cells [10]. This has been shown for HIV [39] but has not yet been elucidated for coronaviruses [40]. Another is their heterogeneity, since EVs are diverse in origin, size, composition, and functional characteristics; therefore, the choice of their source for therapeutic use should be carefully elaborated.…”

Development of HiBiT-Tagged Recombinant Infectious Bronchitis Coronavirus for Efficient in vitro and in vivo Viral Quantification

“…Similar considerations also apply to the EVs released during coronavirus infection. EVs are lipid bilayer-enclosed structures released by cells into the extracellular environment, which can be divided into three subgroups: exosomes (30–150 nm), microvesicles (50–1,000 nm) and apoptotic bodies (50 nm to 5 μm) (Giannessi et al, 2020 ). It has been shown that infections caused by HIV and HCV induce the release of EVs to create a proviral environment, but the relationship between coronaviruses and EVs is not fully characterized (Giannessi et al, 2020 ).…”

“…EVs are lipid bilayer-enclosed structures released by cells into the extracellular environment, which can be divided into three subgroups: exosomes (30–150 nm), microvesicles (50–1,000 nm) and apoptotic bodies (50 nm to 5 μm) (Giannessi et al, 2020 ). It has been shown that infections caused by HIV and HCV induce the release of EVs to create a proviral environment, but the relationship between coronaviruses and EVs is not fully characterized (Giannessi et al, 2020 ). In one study, overexpressed SARS-CoV S protein was not readily detected in the pelleted exosomes, unless the transmembrane and cytoplasmic domains were replaced by those of VSV-G (Kuate et al, 2007 ).…”

“…In theory, some of the VLPs can be separated from infectious virions using density gradient ultracentrifugation. But due to their remarkable resemblance, there is no reliable method to completely separate infectious particles from contaminating VLPs and EVs (Giannessi et al, 2020 ). Therefore, the supernatant RLU value measured in this study only serves as a quick surrogate readout of the IBV replication level, and the number of infectious particles has to be determined by assays like TCID50 or plaque assay.…”

Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

“…Human host factor angiotensin-converting enzyme 2 (ACE2) has been identified, during the first coronavirus epidemic, as the receptor for the SARS causing coronavirus [ 129 ]. ACE2 and the DC-SIGN family of receptors bind the S protein, mediating coronavirus entry to target cells [ 125 ].…”