Quasi-enveloped hepatitis virus assembly and release

Feng, Zongdi

doi:10.1016/bs.aivir.2020.08.004

Cited by 10 publications

(9 citation statements)

References 68 publications

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“…However, they do not have viral glycoproteins on the membrane surface, the latter being the main feature of conventional enveloped viruses. They are non-lytically secreted from infected cells as small extracellular vesicles and are found in the blood of infected patients, or the supernatant of infected cell cultures [ 128 ]. It is not clear which cell types begin the infection, which is preferentially transmitted by the fecal-oral route and rarely via blood transfusion [ 129 ].…”

Section: Natural Compounds Against Rna Virusesmentioning

confidence: 99%

Antiviral Activity Exerted by Natural Products against Human Viruses

Musarra‐Pizzo

Pennisi

Ben-Amor

et al. 2021

Viruses

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Viral infections are responsible for several chronic and acute diseases in both humans and animals. Despite the incredible progress in human medicine, several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are still associated with high morbidity and mortality rates in humans. Natural products from plants or other organisms are a rich source of structurally novel chemical compounds including antivirals. Indeed, in traditional medicine, many pathological conditions have been treated using plant-derived medicines. Thus, the identification of novel alternative antiviral agents is of critical importance. In this review, we summarize novel phytochemicals with antiviral activity against human viruses and their potential application in treating or preventing viral disease.

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Section: Natural Compounds Against Rna Virusesmentioning

confidence: 99%

Antiviral Activity Exerted by Natural Products against Human Viruses

Musarra‐Pizzo

Pennisi

Ben-Amor

et al. 2021

Viruses

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“…It has been shown in many studies that both enveloped and non-enveloped viruses can be detected in exosomes. Similar to previously detected quasienveloped hepatitis A virus and hepatitis E virus, the identification of these host exosomal membrane wrapped HBV particles in this study blurs the classical concept of enveloped HBV particles and potentially alters the traditional understanding on HBV life cycle [316].…”

Section: Infectious Ability Of the Hbv Hijacked Exosomessupporting

confidence: 77%

Analysis of the relevance of exosomes for the spread of hepatitis B virus

Wu¹

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As one of the most widespread infectious diseases in the world, it is currently estimated that approximately 296 million people globally are chronically infected with Hepatitis B virus (HBV), the consequences of HBV infection cause more than 620,000 deaths each year. Although safe and effective HBV vaccines have reduced the incidence of new HBV infections in most countries, there are still around 1.5 million new infections each year. HBV remains a major health problem because there is no large-scale effective vaccination strategy in many countries with a high burden of disease, many people with chronic HBV infection are not receiving effective and timely treatment, and a complete cure for chronic infection is still far from being achieved. Since its discovery, HBV has been identified as an enveloped DNA virus with a diameter of 42 nm. For efficient egress from host cells, HBV is thought to acquire the viral envelope by budding into multivesicular bodies (MVBs) and escape from infected cells via the exosome release pathway. It is clear that HBV hijacks the host vesicle system to complete self-assembly and propagation by interacting with factors that mediate exosome formation. Consequently, the overlap with exosome biogenesis, using MVBs as the release platform, raises the possibility for the release of exosomal HBV particles. Currently, virus containing exosomal vesicles have been described for several viruses. In light of this, this study explored whether intact HBV-virions wrapped in exosomes are released by HBV-producing cells. First, this study established a robust method for efficient separation of exosomes from HBV virions by a combination of differential ultracentrifugation and iodixanol density gradient centrifugation. Fractionation of the density gradient revealed that two populations of infectious viral particles can be separated from the culture fluids of HBV-producing cells. The population present in the low-density peak co-migrates with the exosome markers. Whereas the population that appeared in the high-density fractions was the classical HBV virions, which are rcDNA-containing nucleocapsids encapsulated by the HBV envelope. Subsequently, the characterization of this low-density population was performed, namely the highly purified exosome fraction was systematically investigated. Relying on the detergent sensitivity of the exosome membrane and the outer envelope of the HBV virus, disruption of the exosome structure by treatment with limited detergent revealed the presence of HBsAg in the exosomes. At the same time, mild and limited NP-40 treatment of highly purified exosomes and a further combination of density gradient centrifugation resulted in the stepwise release of intact HBV virions and naked capsids from the exosomes generated by HBV-producing cells. This implies the presence of intact HBV particles encapsulated by the host membrane. The presence of exosome-encapsulated HBV particles was consequently also verified by suppressing the morphogenesis of MVBs or exosomes. Impairment of MVB- or exosome-generation with small molecule inhibitors has significantly inhibited the release of host membrane-encapsulated HBV particles as well. Likewise, silencing of exosome-related proteins caused a diminution of exosome output, which compromised the budding efficiency of wrapped HBV. Moreover, electron microscopy images of ultra-thin sections combined with immunogold staining visualized the hidden virus in the exosomal structure. Additionally, the presence of LHBs on the surface of exosomes derived from HBV-expressing cells was also observed. As expected, these exosomal membrane-wrapped HBV particles can spread productive infection in differentiated HepaRG cells. In HBV-susceptible cells, as LHBs on the membrane surface, this type of exosomal HBV appeared to be uptaken in an NTCP receptor-dependent manner. Taken together these data indicate that a fraction of intact HBV virions can be released as exosomes. This reveals a so far not described release pathway for HBV. Exosomes hijacked by HBV act as a transporter impacting the dissemination of the virus.

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“…Like the previous detection of quasi-enveloped HAV and hepatitis E viruses, the discovery of these host membrane-cloaked HBV blurs the classic definition of HBV-enveloped particles and might change the conventional understanding on the life cycle of HBV. 43 We describe here that the cell culture supernatant of HBV-expressing hepatoma cells contains 2 infectious populations with distinctly different buoyant density. Limited detergent treatment of the fraction with lower density caused successive release of the Dane particles, which can be further processed to naked capsids.…”

Section: Discussionmentioning

confidence: 93%