Research Highlights

Virus-cell interaction: An oxygen offer to SV40

NeuAc (top) and NeuGc (bottom), the most prevalent sialic acids found in mammalian cells. The only difference between the two is the additional oxygen atom (blue) in the N-glycolyl group of NeuGc. From Varki, A. Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins. Nature 446, 1023-1029 (2007).

Although latent SV 40 infection is mostly symptomless in humans, it is known to cause kidney disease in apes and it is suspected that it may also contribute to human tumor development. Similar to its close relatives murine polyoma virus (Py) and human BK viruses, SV40 binds to target cells by interacting with sialic acid-containing glycolipids (gangliosides) on the host cell. Reporting in the Journal of Virology, Ten Feizi and colleagues now elucidate the details of SV40-sialic acid binding.

To examine the interaction between SV40 and surface glycolipids, the authors created a glycan microarray containing a broad range of lipid-linked oligosaccharide probes. SV40 preferentially bound to GM1 that terminates in NeuGc rather NeuAc; binding was not influenced by composition of the gangliosides' lipid component. These findings indicate that for host cell binding SV40 prefers the sialic acid NeuGc, which differs chemically from NeuAc in having an extra oxygen atom, resulting from the hydroxylation of the acyl group bound to the hexose ring (CH₂OH instead of CH₃; see figure).

Upon generating a model of the SV40 protein VP1 bound to sialyllactose, Feizi and colleagues found that the glycolyl group of NeuGc makes two contacts with Gln 62 of VP1, whereas the NeuAc acetyl group cannot interact with this residue. In contrast to SV40, in Py neither NeuGc nor NeuAc can establish hydrogen bonds with the analogous residue (Tyr 72); therefore, Py binding to target cells is indifferent to the acyl substituent on the hexose ring of the cell surface glycolipid.

Humans have lost the ability to synthesize NeuGc as they have a non-functional hydrolase enzyme. In addition to the lack of the linear blood group B-like -galactose antigen, the absence of NeuGc separates humans from all other mammalian species, including primates. One plausible evolutionary hypothesis suggests that the NeuGc loss was evolutionarily favorable, as it hindered the ability of a range of pathogens to bind to human cells. The presented study supports this hypothesis by revealing that SV40 preferentially binds to NeuGc. Future studies may uncover additional nuances in the functional consequences of sialic acid diversity on host-virus interactions.

Author: Mirko von Elstermann