Unconventional secretion of hepatitis A virus

Kirkegaard, Karla

doi:10.1073/pnas.1707142114

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…4j). In order to study directional HAV release, it will be interesting to examine natural HAV isolates, which do not appear to lyse infected cells 40 .…”

Section: Resultsmentioning

confidence: 99%

Stem cell-derived polarized hepatocytes

Thi

Belote

et al. 2020

Nat Commun

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Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver biology. Despite their numerous advantages, HLCs lack critical in vivo characteristics, including cell polarity. Here, we report a stem cell differentiation protocol that uses transwell filters to generate columnar polarized HLCs with clearly defined basolateral and apical membranes separated by tight junctions. We show that polarized HLCs secrete cargo directionally: Albumin, urea, and lipoproteins are secreted basolaterally, whereas bile acids are secreted apically. Further, we show that enterically transmitted hepatitis E virus (HEV) progeny particles are secreted basolaterally as quasi-enveloped particles and apically as naked virions, recapitulating essential steps of the natural infectious cycle in vivo. We also provide proof-of-concept that polarized HLCs can be used for pharmacokinetic and drug-drug interaction studies. This novel system provides a powerful tool to study hepatocyte biology, disease mechanisms, genetic variation, and drug metabolism in a more physiologically relevant setting.

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“…4j). In order to study directional HAV release, it will be interesting to examine natural HAV isolates, which do not appear to lyse infected cells 40 .…”

Section: Resultsmentioning

confidence: 99%

Stem cell-derived polarized hepatocytes

Thi

Belote

et al. 2020

Nat Commun

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“…Particles of HAV, hepatitis E and BTV have also been observed surrounded by membranes [195],[243,244]. Nevertheless, the precise secretion mechanism of these “non-enveloped” viruses has to be defined individually, as other unconventional secretion mechanisms beyond autophagy-based have been reported [245]. As described above, in the case of non-lytic release of HAV and BTV, an ESCRT-mediated, exosome-like mechanism involving budding into MVBs has been identified [195-197].…”

Section: Autophagy Pathway (Figure 5)mentioning

confidence: 99%

Viral journeys on the intracellular highways

Robinson

Schor

Barouch-Bentov

et al. 2018

Cell. Mol. Life Sci.

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Viruses are obligate intracellular pathogens that are dependent on cellular machineries for their replication. Recent technological breakthroughs have facilitated reliable identification of host factors required for viral infections and better characterization of the virus-host interplay. While these studies have revealed cellular machineries that are uniquely required by individual viruses, accumulating data also indicate the presence of broadly required mechanisms. Among these overlapping cellular functions are components of intracellular membrane trafficking pathways. Here, we review recent discoveries focused on how viruses exploit intracellular membrane trafficking pathways to promote various stages of their life cycle, with an emphasis on cellular factors that are usurped by a broad range of viruses. We describe broadly required components of the endocytic and secretory pathways, the Endosomal Sorting Complexes Required for Transport pathway, and the autophagy pathway. Identification of such overlapping host functions offers new opportunities to develop broad-spectrum host-targeted antiviral strategies.

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“…In addition to the classical view of single virus infectious unit of picornaviruses, structures containing many viral genomes support the existence of collective infectious units (Sanjuán, 2017). Lipid vesicles have been observed in HAV and EV infections (Feng et al, 2013; Chen et al, 2015; Kirkegaard, 2017). This current evidence incorporates the vesicle release and transmission to the standard lytic release and transmission of free virions, opening the debate on the “social evolution” of picornaviruses.…”

Section: Population Dynamics and Genetic Variabilitymentioning

confidence: 99%

Evolutionary and Structural Overview of Human Picornavirus Capsid Antibody Evasion

Cifuente

Moratorio

2019

Front. Cell. Infect. Microbiol.

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Picornaviruses constitute one of the most relevant viral groups according to their impact on human and animal health. Etiologic agents of a broad spectrum of illnesses with a clinical presentation that ranges from asymptomatic to fatal disease, they have been the cause of uncountable epidemics throughout history. Picornaviruses are small naked RNA-positive single-stranded viruses that include some of the most important pillars in the development of virology, comprising poliovirus, rhinovirus, and hepatitis A virus. Picornavirus infectious particles use the fecal–oral or respiratory routes as primary modes of transmission. In this regard, successful viral spread relies on the capability of viral capsids to (i) shelter the viral genome, (ii) display molecular determinants for cell receptor recognition, (iii) facilitate efficient genome delivery, and (iv) escape from the immune system. Importantly, picornaviruses display a substantial amount of genetic variability driven by both mutation and recombination. Therefore, the outcome of their replication results in the emergence of a genetically diverse cloud of individuals presenting phenotypic variance. The host humoral response against the capsid protein represents the most active immune pressure and primary weapon to control the infection. Since the preservation of the capsid function is deeply rooted in the virus evolutionary dynamics, here we review the current structural evidence focused on capsid antibody evasion mechanisms from that perspective.

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Unconventional secretion of hepatitis A virus

Cited by 6 publications

References 16 publications

Stem cell-derived polarized hepatocytes

Stem cell-derived polarized hepatocytes

Viral journeys on the intracellular highways

Evolutionary and Structural Overview of Human Picornavirus Capsid Antibody Evasion

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