HCV egress – unconventional secretion of assembled viral particles

After their assembly by budding into the lumen of the intermediate compartment (IC) at the endoplasmic reticulum (ER)–Golgi interface, coronaviruses (CoVs) are released from their host cells following a pathway that remains poorly understood. The traditional view that CoV exit occurs via the constitutive secretory route has recently been questioned by studies suggesting that this process involves unconventional secretion. Here, using the avian infectious bronchitis virus (IBV) as a well-established model virus, we have applied confocal microscopy to investigate the pathway of CoV egress from epithelial Vero cells. We report a novel effect of IBV infection on cellular endomembranes, namely, the compaction of the pericentrosomal endocytic recycling compartment (ERC) defined by the GTPase Rab11, which coincides with the previously described Golgi fragmentation, as well as virus release. Despite Golgi disassembly, the IC elements containing the major IBV membrane protein (M)—which mostly associates with newly formed virus particles—maintain their close spatial connection with the Rab11-positive endocytic recycling system. Moreover, partial colocalization of the M protein with Rab11 was observed, whereas M displayed negligible overlap with LAMP-1, indicating that IBV egress does not occur via late endosomes or lysosomes. Synchronization of virus release using temperature-shift protocols was accompanied by increased colocalization of M and Rab11 in vesicular and vacuolar structures in the pericentrosomal region and at the cell periphery, most likely representing IBV-containing transport carriers. In conclusion, these results add CoVs to the growing list of viruses exploiting the endocytic recycling apparatus defined by Rab11 for their assembly and/or release.

show abstract

“… 2012 ; Bunz et al. 2021 ). Bunyaviruses, which, like CoVs, assemble by budding at IC/Golgi membranes (Jäntti et al.…”

Section: Discussionmentioning

confidence: 99%

Evidence for the role of Rab11-positive recycling endosomes as intermediates in coronavirus egress from epithelial cells

Saraste

Enyioko

Dale

et al. 2022

Histochem Cell Biol

View full text Add to dashboard Cite

show abstract

“…In this phenomenon, viruses take advantage of the host ESCRT machinery to acquire a protective membrane and exit the infected cell without lysis, avoiding then the recognition by the host immune system (Feng et al, 2014). This behavior, first reported in hepatitis A virus (HAV) (Feng et al, 2013;Jiang et al, 2020), was found also in hepatitis E virus (HEV) (Nagashima et al, 2014), Coxsackie B virus (CBV) (Sin et al, 2017), but also in enveloped viruses, like hepatitis C virus (HCV) (Bunz et al, 2022) and others. Furthermore, the "Trojan exosome" hypothesis states that retroviruses, like human immunodeficiency virus (HIV), use EVs biogenesis pathways for their egression, spread and uptake, enhancing their infectivity and modulating host gene expression and immune responses (Hildreth, 2017;Chen et al, 2021).…”

Section: Evs and Viral Infections: A Multifaceted Interplaymentioning

confidence: 97%

“…Furthermore, the "Trojan exosome" hypothesis states that retroviruses, like human immunodeficiency virus (HIV), use EVs biogenesis pathways for their egression, spread and uptake, enhancing their infectivity and modulating host gene expression and immune responses (Hildreth, 2017;Chen et al, 2021). Another model proposes the "secretory autophagy" for virus non-cytolytic egression from the infected cell through LC3-positive vesicles, originating from autophagosomes fusing with the plasma membrane instead of lysosomes (Altan-Bonnet, 2016;Bunz et al, 2022). According to this model, first described by Chen YH et al, multiple viral particles are selectively captured by LC3-positive "autophagosome-like" organelles, enriched in phosphatidylserine lipids, and released non-cytolitically from the infected cells (Chen et al, 2015).…”

Section: Evs and Viral Infections: A Multifaceted Interplaymentioning

confidence: 99%

“…According to these, extracellular vesicles (EVs) trafficking seems to be a deeply involved pathway in SARS-CoV-2 infection, contributing to viral replication, immune evasion, egression from infected cells, and spread to other cell targets, through the so-called "replicative organelles" (Pleet et al, 2018;. Several hypotheses further support a role of EVs in SARS-CoV-2 infection, like the existence of "quasi-enveloped viruses" (Feng et al, 2014), the "Trojan exosome" hypothesis (Hildreth, 2017), and the "secretory autophagy" model (Bunz et al, 2022), but none of these has been confirmed as the prevalent and further investigations are needed. EVs are well known as membraneenveloped, nano-and micro-sized particles secreted by different cell types, distinct in their size, composition and function according to their biogenesis, delivering different cargoes to distant targets and thus affecting intercellular signaling (Kalluri and LeBleu, 2020).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SARS-CoV-2 and extracellular vesicles: An intricate interplay in pathogenesis, diagnosis and treatment

Sbarigia

Vardanyan

Buccini

et al. 2022

Front. Nanotechnol.

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are widely recognized as intercellular communication mediators. Among the different biological processes, EVs play a role in viral infections, supporting virus entrance and spread into host cells and immune response evasion. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became an urgent public health issue with significant morbidity and mortality worldwide, being responsible for the current COVID-19 pandemic. Since EVs are implicated in SARS-CoV-2 infection in a morphological and functional level, they have gained growing interest for a better understanding of SARS-CoV-2 pathogenesis and represent possible diagnostic tools to track the disease progression. Furthermore, thanks to their biocompatibility and efficient immune activation, the use of EVs may also represent a promising strategy for the development of new therapeutic strategies against COVID-19. In this review, we explore the role of EVs in viral infections with a focus on SARS-CoV-2 biology and pathogenesis, considering recent morphometric studies. The common biogenesis aspects and structural similarities between EVs and SARS-CoV-2 will be examined, offering a panoramic of their multifaceted interplay and presenting EVs as a machinery supporting the viral cycle. On the other hand, EVs may be exploited as early diagnostic biomarkers and efficient carriers for drug delivery and vaccination, and ongoing studies will be reviewed to highlight EVs as potential alternative therapeutic strategies against SARS-CoV-2 infection.

show abstract

“…Это означает, что для разработки новых средств и, главное, для понимания патогенеза инфекции необходимы более детальные знания жизненного цикла вируса и взаимодействия его с клеточными процессами. Изучение жизненного цикла ВГС показало, что он может высвобождаться из клетки в составе экзосом, пройдя эндосомальный путь [43,44]. В прохождении этого пути участвуют две клеточные системы -ESCRT и комплекс белков семейства Rab [45][46][47][48].…”

Section: экзосомы и вирус гепатита вunclassified

Exosomes in the life cycle of viruses and the pathogenesis of viral infections

Кущ¹,

Ivanov²

2023

Problems of Virology

View full text Add to dashboard Cite

Exosomes are extracellular vesicles of endosomal origin, with a bilayer membrane, 30160 nm in diameter. Exosomes are released from cells of different origins and are detected in various body fluids. They contain nucleic acids, proteins, lipids, metabolites and can transfer the contents to recipient cells. Exosome biogenesis involves cellular proteins of the Rab GTPase family and the ESCRT system, which regulate budding, vesicle transport, molecule sorting, membrane fusion, formation of multivesicular bodies and exosome secretion. Exosomes are released from cells infected with viruses and may contain viral DNA and RNA, as well as mRNA, microRNA, other types of RNA, proteins and virions. Exosomes are capable of transferring viral components into uninfected cells of various organs and tissues. This review analyzes the impact of exosomes on the life cycle of widespread viruses that cause serious human diseases: human immunodeficiency virus (HIV-1), hepatitis B virus, hepatitis C virus, SARS-CoV-2. Viruses are able to enter cells by endocytosis, use molecular and cellular pathways involving Rab and ESCRT proteins to release exosomes and spread viral infections. It has been shown that exosomes can have multidirectional effects on the pathogenesis of viral infections, suppressing or enhancing the course of diseases. Exosomes can potentially be used in noninvasive diagnostics as biomarkers of the stage of infection, and exosomes loaded with biomolecules and drugs - as therapeutic agents. Genetically modified exosomes are promising candidates for new antiviral vaccines.

show abstract

HCV egress – unconventional secretion of assembled viral particles

Cited by 12 publications

References 107 publications

Evidence for the role of Rab11-positive recycling endosomes as intermediates in coronavirus egress from epithelial cells

Evidence for the role of Rab11-positive recycling endosomes as intermediates in coronavirus egress from epithelial cells

SARS-CoV-2 and extracellular vesicles: An intricate interplay in pathogenesis, diagnosis and treatment

Exosomes in the life cycle of viruses and the pathogenesis of viral infections

Contact Info

Product

Resources

About