Sialic acids as receptor determinants for coronaviruses

Schwegmann-Weßels, Christel; Herrler, Georg

doi:10.1007/s10719-006-5437-9

Cited by 158 publications

(162 citation statements)

References 63 publications

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“…1, step 1) would have affected relative efficacy of interactions of various pathogens with humans. Humans should be resistant to pathogens binding Neu5Gc (32)(33)(34)(35)(36) and more susceptible to pathogens preferring to bind Neu5Ac. Particularly interesting is a difference in erythrocyte Sia-binding preference between malarial parasites of humans and African NHHs (36).…”

Section: Human-specific Neu5gc Loss Affects Pathogen Regimesmentioning

confidence: 99%

Uniquely human evolution of sialic acid genetics and biology

Varki

2010

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

249

248

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Darwinian evolution of humans from our common ancestors with nonhuman primates involved many gene-environment interactions at the population level, and the resulting human-specific genetic changes must contribute to the "Human Condition." Recent data indicate that the biology of sialic acids (which directly involves less than 60 genes) shows more than 10 uniquely human genetic changes in comparison with our closest evolutionary relatives. Known outcomes are tissue-specific changes in abundant cell-surface glycans, changes in specificity and/or expression of multiple proteins that recognize these glycans, and novel pathogen regimes. Specific events include Alu-mediated inactivation of the CMAH gene, resulting in loss of synthesis of the Sia N-glycolylneuraminic acid (Neu5Gc) and increase in expression of the precursor N-acetylneuraminic acid (Neu5Ac); increased expression of α2-6-linked Sias (likely because of changed expression of ST6GALI); and multiple changes in SIGLEC genes encoding Sia-recognizing Ig-like lectins (Siglecs). The last includes binding specificity changes (in ; expression pattern changes (in Siglecs -1, -5, -6, and -11); gene conversion (SIGLEC11); and deletion or pseudogenization (SIGLEC13, SIGLEC14, and SIGLEC16). A nongenetic outcome of the CMAH mutation is human metabolic incorporation of foreign dietary Neu5Gc, in the face of circulating anti-Neu5Gc antibodies, generating a novel "xeno-auto-antigen" situation. Taken together, these data suggest that both the genes associated with Sia biology and the related impacts of the environment comprise a relative "hot spot" of genetic and physiological changes in human evolution, with implications for uniquely human features both in health and disease.genomics | Siglec | Neu5Gc | Xeno-auto-antigen

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Section: Human-specific Neu5gc Loss Affects Pathogen Regimesmentioning

confidence: 99%

Uniquely human evolution of sialic acid genetics and biology

Varki

2010

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

249

248

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“…Mouse hepatitis coronavirus (MHV) from ␤-genus recognizes carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (13,14), although certain MHV strains also recognize heparan sulfate (15,16). Some coronaviruses from each of the three genera recognize sugars (17)(18)(19)(20). MERS-CoV belongs to the ␤-genus and uses human dipeptidyl peptidase 4 (DPP4) as its host receptor (21).…”

mentioning

confidence: 99%

Crystal Structure of the Receptor-Binding Domain from Newly Emerged Middle East Respiratory Syndrome Coronavirus

Chen

Rajashankar

Yang

et al. 2013

J Virol

118

123

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The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans. Since the summer of 2012, a novel coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged from the Middle East and spread to parts of Europe. MERS-CoV infection often leads to acute pneumonia and renal failure, and the human fatality rate is more than 50% (1, 2). To date, MERS-CoV has infected at least 77 people and was able to be transmitted from human to human. The genomic sequence of MERS-CoV is closely related to the sequences of certain bat coronaviruses (3-5), raising concerns over persistent bat-to-human cross-species transmission of the virus. The clinical signs and epidemic patterns of MERS-CoV are reminiscent of the severe acute respiratory syndrome coronavirus (SARS-CoV), the etiological agent of the worldwide SARS epidemic in 2002-2003 that infected more than 8,000 people with a ϳ10% fatality rate (6, 7). MERS-CoV poses a significant threat to global health and economy.Coronaviruses are enveloped and positive-stranded RNA viruses and can be divided into three major genera, ␣, ␤, and ␥ (8). They mainly cause respiratory, gastrointestinal, and central nervous system diseases in mammals and birds. Coronaviruses recognize a variety of host receptors. Human NL63 respiratory coronavirus (HCoV-NL63) from ␣-genus and SARS-CoV from ␤-genus both recognize angiotensin-converting enzyme 2 (ACE2) as their host receptor (9, 10). Porcine respiratory coronavirus (PRCV) and some other coronaviruses from ␣-genus recognize aminopeptidase N (APN) (11, 12). Mouse hepatitis coronavirus (MHV) from ␤-genus recognizes carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (13, 14), although certain MHV strains also recognize heparan sulfate (15, 16). Some coronaviruses from each of the three genera recognize sugars (17-20). MERS-CoV belongs to the ␤-genus and uses human dipeptidyl peptidase 4 (DPP4) as its host receptor (21). Receptor recognition is a major determinant of coronavirus host range and tropism.An envelope-anchored trimeric spike p...

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“…Other respiratory pathogens, such as parainfluenza viruses (9), some coronaviruses (10), and Streptococcus pneumoniae (11), also use sialic acid as a receptor. Human influenza viruses such as the 2009 pandemic H1N1 virus recognize α-2,6-linked sialic acid receptors present in the upper respiratory tract, whereas avian influenza viruses such as H5N1 predominantly recognize α-2,3-linked sialic acid receptors, which are present in the human lower respiratory tract as well (12,13).…”

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confidence: 99%

Prevention of influenza by targeting host receptors using engineered proteins

Connaris

Govorkova

Ligertwood

et al. 2014

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

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Significance We have developed a new class of host-targeted biologics to prevent influenza by engineering multivalent carbohydrate-binding modules that bind with high affinity to sialic acid, the critical component of the influenza virus cell surface receptor. Mouse studies reveal a remarkable efficacy: a single 1-μg dose of the lead biologic given 7 d before a lethal challenge with 2009 pandemic H1N1 influenza virus provides complete protection. This new approach has the potential to be a front-line defense against any current and future influenza virus, overcoming viral escape to vaccines and antivirals. In addition, the biologics may have broader application against other respiratory pathogens.

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Sialic acids as receptor determinants for coronaviruses

Cited by 158 publications

References 63 publications

Uniquely human evolution of sialic acid genetics and biology

Uniquely human evolution of sialic acid genetics and biology

Crystal Structure of the Receptor-Binding Domain from Newly Emerged Middle East Respiratory Syndrome Coronavirus

Prevention of influenza by targeting host receptors using engineered proteins

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