Coronaviruses Induce Entry-Independent, Continuous Macropinocytosis

Freeman, Megan Culler; Peek, Christopher T.; Becker, Michelle M.; Smith, Everett Clinton; Denison, Mark R.

doi:10.1128/mbio.01340-14

Cited by 58 publications

(54 citation statements)

References 52 publications

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“…In such a scenario, viruses are recycled to the cell surface or degraded intracellularly. Interestingly, it was shown for MHV and SARS-CoV that endocytosis may play a role in cell-to-cell spread and micropinocytosis 51 , but one may assume that it may differ between these species.…”

Section: Discussionmentioning

confidence: 99%

Early events during human coronavirus OC43 entry to the cell

Owczarek

Szczepański

Milewska

et al. 2018

Sci Rep

108

100

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The Coronaviridae family clusters a number of large RNA viruses, which share several structural and functional features. However, members of this family recognize different cellular receptors and exploit different entry routes, what affects their species specificity and virulence. The aim of this study was to determine how human coronavirus OC43 enters the susceptible cell. Using confocal microscopy and molecular biology tools we visualized early events during infection. We found that the virus employs caveolin-1 dependent endocytosis for the entry and the scission of virus-containing vesicles from the cell surface is dynamin-dependent. Furthermore, the vesicle internalization process requires actin cytoskeleton rearrangements. With our research we strove to broaden the understanding of the infection process, which in future may be beneficial for the development of a potential therapeutics.

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Section: Discussionmentioning

confidence: 99%

Early events during human coronavirus OC43 entry to the cell

Owczarek

Szczepański

Milewska

et al. 2018

Sci Rep

108

100

View full text Add to dashboard Cite

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“…Given the frequent propensity of coronaviruses, including SARS-CoV-1, to lead to fused cells in vitro, our observation that isolated virus from the AGMs form syncytia in Vero-E6 cells (Fig. 1A) and the observation of multinucleated syncytial cells in human cases of disease (24,25), this finding is likely a viral cytopathic effect. Moreover, the Peyer's patches from 5 out of 6 AGMs contained some of the highest levels of vRNA ( Fig.…”

Section: Sars-cov-2 Vrna Was Detected Throughout Respiratory and Gastmentioning

confidence: 91%

SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts

Hartman

Nambulli

McMillen

et al. 2020

Preprint

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Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green monkeys (AGM) with a low passage human isolate of SARS-CoV-2 by aerosol or mucosal exposure resulted in mild clinical infection with a transient decrease in lung tidal volume. Imaging with human clinical-

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“…It is therefore plausible that HCoV patient sera targeting the S2 also neutralise, without affecting binding to ACE2, by interfering with alternative routes of viral entry. Indeed, entry of SARS-CoV-2 can also be facilitated by the alternative receptor CD147, also known as Basigin (BSG) 28 and possibly also by receptor-independent mechanisms, as has been described for other CoVs 29,30 .…”

mentioning

confidence: 88%

Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans

Ng¹,

Faulkner²,

Cornish³

et al. 2020

Preprint

126

170

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Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections 1 . Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 , is a recent zoonotic infection that has quickly reached pandemic spread 2,3 . Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 Spike (S) glycoprotein, we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies, exclusively of the IgG class, were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals with recent HCoV infection and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 Sreactive IgG antibodies, as well as concomitant IgM and IgA antibodies throughout the observation period of 6 weeks since symptoms onset. HCoV patient sera also variably reacted with SARS-CoV-2 S and nucleocapsid (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, HCoV patient sera exhibited specific neutralising activity against SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for serology, seroprevalence and vaccine studies, as well as for our understanding of susceptibility to and natural course of SARS-CoV-2 infection. ResultsImmune cross-reactivity among seasonally spreading human coronaviruses (HCoVs) has long been hypothesised to provide cross-protection, albeit transient, against infection with distinct HCoV types 1,4,5 . To determine the degree of cross-reactivity between HCoVs and the recently introduced zoonotic coronavirus SARS-CoV-2, we developed a sensitive flow cytometry-based assay for detection of SARS-CoV-2-binding antibodies. Sera from COVID-19 patients at University College London Hospitals (UCLH) (Table S1), contained high levels of IgG, IgM and IgA antibodies recognising the wild-type Spike (S) glycoprotein of SARS-CoV-2 expressed on the surface of HEK293T cells, whereas control sera did not (Fig. 1a). Notably, sera from a proportion patients with confirmed HCoV infection collected before or during the early spread of SARS-CoV-2 in the UK (Table S1), also contained SARS-CoV-2 S-specific antibodies (Fig. 1a). However, the latter sera contained only lower levels of S-specific IgG and no IgM or IgA antibodies, which clearly distinguished them from COVID-19 patient sera (Fig. 1a). The SARS-CoV-2 S protein is proteolytically processed into the S1 and S2 subunits that mediate target cell attachment and entry, respectively 6,7 . S2 exhibits a higher degree of homology among coronaviruses than S1 (Extended data Fig. 1...

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Coronaviruses Induce Entry-Independent, Continuous Macropinocytosis

Cited by 58 publications

References 52 publications

Early events during human coronavirus OC43 entry to the cell

Early events during human coronavirus OC43 entry to the cell

SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts

Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans

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