Significance of lysosomes in the morphogenesis of coronaviruses

Ducatelle, Richard; Hoorens, J.

doi:10.1007/bf01314299

Cited by 23 publications

(18 citation statements)

References 15 publications

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“…Since the 1960's, intact coronaviruses have been reported in lysosomes at late stages of infection (Ducatelle and Hoorens 1984) but the significance of these observations remained unknown in terms of viral dynamics. Here we demonstrated that coronaviruses egress from infected cells by tracking a singular path through lysosomes and then to the surface.…”

Section: Discussionmentioning

confidence: 99%

β-Coronaviruses use lysosomal organelles for cellular egress

Altan‐Bonnet

Ghosh

et al. 2020

Preprint

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Abstractβ-Coronaviruses are a family of positive-strand enveloped RNA viruses that include the severe acute respiratory syndrome-CoV2 (SARS-CoV2). While much is known regarding their cellular entry and replication pathways, their mode of egress remains uncertain; however, this is assumed to be via the biosynthetic secretory pathway by analogy to other enveloped viruses. Using imaging methodologies in combination with virus-specific reporters, we demonstrate that β-Coronaviruses utilize lysosomal trafficking for egress from cells. This pathway is regulated by the Arf-like small GTPase Arl8b; thus, virus egress is insensitive to inhibitors of the biosynthetic secretory pathway. Coronavirus infection results in lysosome deacidification, inactivation of lysosomal degradation and disruption of antigen presentation pathways. This coronavirus-induced exploitation of lysosomes provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.

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Section: Discussionmentioning

confidence: 99%

β-Coronaviruses use lysosomal organelles for cellular egress

Altan‐Bonnet

Ghosh

et al. 2020

Preprint

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“…The first report showing the relevance of endosome-lysosome in CoVs was from a morphological study in which two CoVs (IBV and Porcine Epidemic Diarrhea Virus (PEDV)) were found to accumulate in the lysosomes of cells after infection [36], indicating that the possible functional implication of lysosome in CoVs infection. Subsequent studies have firmly established that the endocytic pathway is the key mechanisms controlling the entry of CoVs into the host cells, and thus the endocytic pathway has been widely investigated as the target of anti-viral therapies, as summarized in Table 2.…”

Section: Involvement Of the Endocytic Pathway In Covs Infectionmentioning

confidence: 99%

Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19

Yang¹,

Shen²

2020

Int. J. Biol. Sci.

393

444

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Coronaviruses (CoVs) are a group of enveloped, single-stranded positive genomic RNA viruses and some of them are known to cause severe respiratory diseases in human, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the ongoing coronavirus disease-19 (COVID-19). One key element in viral infection is the process of viral entry into the host cells. In the last two decades, there is increasing understanding on the importance of the endocytic pathway and the autophagy process in viral entry and replication. As a result, the endocytic pathway including endosome and lysosome has become important targets for development of therapeutic strategies in combating diseases caused by CoVs. In this mini-review, we will focus on the importance of the endocytic pathway as well as the autophagy process in viral infection of several pathogenic CoVs inclusive of SARS-CoV, MERS-CoV and the new CoV named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and discuss the development of therapeutic agents by targeting these processes. Such knowledge will provide important clues for control of the ongoing epidemic of SARS-CoV-2 infection and treatment of COVID-19.

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“…The role of lysosomes and related acidic compartments in the replication of coronaviruses is not well understood. Coronavirus infection frequently involves the intracellular accumulation of virus-filled, electron-dense structures which have been interpreted to be lysosomes (David-Ferreira andManaker, 1965, Ducatelle andHoorens, 1984). Such structures are observed within 2-3 hr postinoculation and have, therefore, been suggested to be involved in virus uptake (David-Ferreira and Manaker, 1965).…”

Section: Ammoniummentioning

confidence: 99%

Attenuation of murine coronavirus infection by ammonium chloride

et al. 1985

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Ammonium chloride at a concentration of 20 mM delayed by 4-5 hr the production of virus progeny in mouse L-2 cells infected at high multiplicity with mouse hepatitis virus (MHV). This delay was seen in the production of both intracellular and extracellular virus. However, the final titers were similar to those produced by MHV-infected cells maintained in normal medium. The manifestation of virus-induced cell fusion was similarly found to be delayed, but not otherwise decreased in severity, when ammonium chloride was present in the culture medium. Ammonium chloride caused similar delays in production of virus-specific, positive-sense RNAs and of viral polypeptides. The relative proportions and apparent molecular weights of viral RNAs and polypeptides were similar to those found in MHV-infected cells cultured in normal medium. In vitro translation of endogenously produced viral RNAs in cell extracts, prepared from MHV-infected cells, was not inhibited by ammonium chloride. Thus, ammonium chloride has no specific, inhibitory effect on viral protein synthesis. Ammonium chloride did not reduce the number of virus-infected cells in culture, as monitored by infectious center assay. Analysis of early events in MHV infection showed that ammonium chloride did not affect adsorption or internalization of MHV by L-2 cells. However, the subsequent eclipse phase, as monitored by decline in infectivity of internalized virus inoculum proceeded less efficiently in the presence of ammonium chloride. On the basis of the known inhibitory effects of ammonium chloride on lysosomal/endosomal functions, the results suggest an endosomal mechanism of MHV uncoating. Thus the primary effect of ammonium chloride on MHV infection of L-2 cells is to attenuate virus uncoating, thereby chronologically displacing all subsequent virus-encoded functions.

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Significance of lysosomes in the morphogenesis of coronaviruses

Cited by 23 publications

References 15 publications

β-Coronaviruses use lysosomal organelles for cellular egress

β-Coronaviruses use lysosomal organelles for cellular egress

Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19

Attenuation of murine coronavirus infection by ammonium chloride

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