Cellular entry of the SARS coronavirus

Hofmann, Heike; Pöhlmann, Stefan

doi:10.1016/j.tim.2004.08.008

Cited by 239 publications

(240 citation statements)

References 62 publications

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“…The carboxypeptidase ACE2 is an important component of the renin-angiotensin system, which controls blood pressure (27,28), and ACE2 is required for cardiac function in mice (29). ACE2 expression in lung and intestine (30) explains important aspects of SARS-CoV tropism, and the protein likely plays a central role in SARS-CoV spread (12). However, it is unclear how the virus induces disease and whether the way it engages ACE2 contributes to this process.…”

Section: Discussionmentioning

confidence: 99%

“…In general, the functional organization of CoV S proteins is similar to that of glycoproteins from several unrelated viruses (12), such as retroviruses, and the SARS-CoV-S protein can be incorporated into the membrane of retroviral particles (13). These so called pseudovirions (''pseudotypes'') accurately mimic receptor engagement and membrane fusion of SARS-CoV and can be used to study S function (13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

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Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Hofmann

Pyrć

Hoek

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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745

699

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Coronavirus (CoV) infection of humans is usually not associated with severe disease. However, discovery of the severe acute respiratory syndrome (SARS) CoV revealed that highly pathogenic human CoVs (HCoVs) can evolve. The identification and characterization of new HCoVs is, therefore, an important task. Recently, a HCoV termed NL63 was discovered in patients with respiratory tract illness. Here, cell tropism and receptor usage of HCoV-NL63 were analyzed. The NL63 spike (S) protein mediated infection of different target cells compared with the closely related 229E-S protein but facilitated entry into cells known to be permissive to SARS-CoV-S-driven infection. An analysis of receptor engagement revealed that NL63-S binds angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV, and HCoV-NL63 uses ACE2 as a receptor for infection of target cells. Potent neutralizing activity directed against NL63-but not 229E-S protein was detected in virtually all sera from patients 8 years of age or older, suggesting that HCoV-NL63 infection of humans is common and usually acquired during childhood. Here, we show that SARS-CoV shares its receptor ACE2 with HCoV-NL63. Because the two viruses differ dramatically in their ability to induce disease, analysis of HCoV-NL63 might unravel pathogenicity factors in SARS-CoV. The frequent HCoV-NL63 infection of humans suggests that highly pathogenic variants have ample opportunity to evolve, underlining the need for vaccines against HCoVs.C oronaviruses (CoVs) are enveloped RNA viruses that are grouped according to genome sequence and serology (1). Human CoVs (HCoVs) 229E and OC43 are members of groups I and II, respectively, and infection with these viruses is thought to be responsible for Ϸ30% of common-cold cases (1). In contrast, infection with severe acute respiratory syndrome (SARS)-CoV causes a severe respiratory tract illness (RTI) that is fatal in Ϸ10% of infected individuals (2, 3). The factors that determine the pathogenicity of CoVs are incompletely understood; however, a role for the spike (S) protein has been suggested (4). The S proteins of CoVs, which provide virions with a corona-like appearance, mediate infection of target cells and play a central role in viral replication (4). The interaction of CoV S proteins with specific cellular receptors determines, to a large extent, which cells can be infected (5), and the entry process is an attractive target for antiviral therapy (6).Recently, a HCoV termed NL63 was discovered in infants and immunocompromised adults with RTI (7, 8). HCoV-NL63 is a group I CoV and is most closely related to HCoV-229E (7-9). HCoV-229E employs CD13 (aminopeptidase N) as a receptor for infection of target cells (10,11). Because the NL63-and 229E-S proteins share 56% amino acid identity (7), it is conceivable that HCoV-NL63 also engages CD13 for infectious cellular entry. However, the HCoV-NL63-S protein contains a unique, 179-aa sequence at its N terminus that does not share homology with other known CoV proteins and that might alter the re...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Hofmann

Pyrć

Hoek

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

745

699

View full text Add to dashboard Cite

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“…The C-terminal membrane fusion subunits of the respective glycoproteins, which anchor the proteins in the viral membranes, contain the following characteristic architectural elements required for membrane fusion: heptad repeats and a hydrophobic fusion peptide. The figure is adapted from [44,54]. …”

Section: The Filoviral Glycoprotein: Structure and Functionmentioning

confidence: 99%

Host Cell Factors in Filovirus Entry: Novel Players, New Insights

Hofmann-Winkler

Kaup

Pöhlmann

2012

Viruses

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Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP) mediates filovirus entry into host cells. Recent studies revealed important insights into the host cell molecules engaged by GP for cellular entry. The binding of GP to cellular lectins was found to concentrate virions onto susceptible cells and might contribute to the early and sustained infection of macrophages and dendritic cells, important viral targets. Tyrosine kinase receptors were shown to promote macropinocytic uptake of filoviruses into a subset of susceptible cells without binding to GP, while interactions between GP and human T cell Ig mucin 1 (TIM-1) might contribute to filovirus infection of mucosal epithelial cells. Moreover, GP engagement of the cholesterol transporter Niemann-Pick C1 was demonstrated to be essential for GP-mediated fusion of the viral envelope with a host cell membrane. Finally, mutagenic and structural analyses defined GP domains which interact with these host cell factors. Here, we will review the recent progress in elucidating the molecular interactions underlying filovirus entry and discuss their implications for our understanding of the viral cell tropism.

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“…Elucidation of the events involved in SARS coronavirus entry into host cells has resulted in a number of significant findings that have been summarized [1094,1095]. The identification of angiotensin converting enzyme 2 (ACE2) as a host receptor for the SARS CoV has been confirmed [1096,1097] and CD290L, a C-type lectin also known as L-SIGN, DC-SIGNR and DC-SIGN2, has been identified as an additional receptor [1098].…”

Section: Sars Cov Biochemical Pharmacologymentioning

confidence: 99%

Developments in Antiviral Drug Design, Discovery and Development in 2004

Meanwell

Belema²,

Carini³

et al. 2005

CDTID

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This article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. Important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis B, hepatitis C; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus; the respiratory viruses, influenza, respiratory syncytial virus, human metapneumovirus, picornaviruses, measles and the severe acute respiratory syndrome coronavirus; human papilloma virus; rotavirus; Ebola virus and West Nile virus, are reviewed.

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Cellular entry of the SARS coronavirus

Cited by 239 publications

References 62 publications

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Host Cell Factors in Filovirus Entry: Novel Players, New Insights

Developments in Antiviral Drug Design, Discovery and Development in 2004

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