Tulane virus recognizes sialic acids as cellular receptors.

Ming Tan,Pengwei Huang,Xufu Zhang,Weiming Zhong,Christina Quigley,Qiang Fan,Chao Wei,Xi Jiang,John S Klassen,Hao Fang,Ming Xia

doi:10.1038/srep11784

Abstract

The recent discovery that human noroviruses (huNoVs) recognize sialic acids (SAs) in addition to histo-blood group antigens (HBGAs) pointed to a new direction in studying virus-host interactions during calicivirus infection. HuNoVs remain difficult to study due to the lack of an effective cell culture model. In this study, we demonstrated that Tulane virus (TV), a cultivable primate calicivirus, also recognizes SAs in addition to the previously known TV-HBGA interactions. Evidence supporting this discovery includes that TV virions bound synthetic sialoglycoconjugates (SGCs) and that treatment of TV permissive LLC-MK2 cells with either neuraminidases or SA-binding lectins inhibited TV infectivity. In addition, we found that Maackia amurensis leukoagglutinin (MAL), a lectin that recognizes the α-2,3 linked SAs, bound LLC-MK2 cells, as well as TV, by which MAL promoted TV infectivity in cell culture. Our findings further highlight TV as a valuable surrogate for huNoVs, particularly in studying virus-host interactions that may involve two host carbohydrate receptors or co-receptors for infection.

Highlights

The recent discovery that human noroviruses recognize sialic acids (SAs) in addition to histo-blood group antigens (HBGAs) pointed to a new direction in studying virus-host interactions during calicivirus infection
In addition to evidence for Tulane virus (TV) recognizing SGCs by in vitro binding experiments, we have demonstrated in this study that the infection of TV in cell cultures is significantly reduced by treatment of the host cells with either neuraminidases or SA-binding lectins
We found that Maackia amurensis leukoagglutinin (MAL), a commercially available lectin that recognizes α -2,3 linked SAs, increased TV infectivity in cell culture

Summary

Introduction

The recent discovery that human noroviruses (huNoVs) recognize sialic acids (SAs) in addition to histo-blood group antigens (HBGAs) pointed to a new direction in studying virus-host interactions during calicivirus infection. We demonstrated that Tulane virus (TV), a cultivable primate calicivirus, recognizes SAs in addition to the previously known TV-HBGA interactions Evidence supporting this discovery includes that TV virions bound synthetic sialoglycoconjugates (SGCs) and that treatment of TV permissive LLC-MK2 cells with either neuraminidases or SA-binding lectins inhibited TV infectivity. A recent study indicated that huNoVs recognize gangliosides as ligands, in which the sialic acid (SA) components played an important role[38] These data strongly suggest that non-HBGA factors and SA-containing sialoglycoconjugates (SGCs) may be other important host factors for huNoV infection. Within Caliciviridae, feline calicivirus (FCV) from the Vesivirus genus[46], porcine sapovirus (PSaV) from the Sapovirus genus[47], and murine norovirus (MNV) from the Norovirus genus[48] have been shown to recognize SAs as receptors for infection, suggesting that SGCs may be commonly recognized by caliciviruses

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