Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2006;23(1):73–84. doi: 10.1007/s10719-006-5439-7

Localisation and distribution of O-acetylated N-acetylneuraminic acids, the endogenous substrates of the hemagglutinin-esterases of murine coronaviruses, in mouse tissue

Andreas Rinninger 1, Colette Richet 2, Alexandre Pons 3, Guido Kohla 4, Roland Schauer 4, Hans-Christian Bauer 1, Jean-Pierre Zanetta 3, Reinhard Vlasak 1,✉
PMCID: PMC7088067  PMID: 16575524

Abstract

Infections by mouse hepatitis viruses result in disease of the liver, the gastrointestinal tract, respiratory tract, and the central nervous system. Coronaviruses related to mouse hepatitis virus express a hemagglutinin-esterase surface glycoprotein, which specifically hydrolyses either 5-N-acetyl-4-O-acetyl neuraminic acid (Neu4,5Ac2) or 5-N-acetyl-9-O-acetyl neuraminic acid (Neu5,9Ac2). Moreover, these sialic acids represent potential cellular receptor determinants for murine coronaviruses. Until now, the distribution of these sialic acids in mouse brain was not thoroughly investigated. Particularly Neu4,5Ac2 was not yet found in mouse brain. Using a sensitive method of gas chromatography coupled to mass spectrometry in the electron impact mode of ionization this manuscript demonstrates the occurrence of 13 different sialic acids varying in their alkyl and acyl substituents in mouse tissues including 5-N-acetyl-4-O-acetyl-9-O-lactyl-neuraminic acid (Neu4,5Ac29Lt), 5-N-acetyl-9-O-lactyl-neuraminic acid (Neu5Ac9Lt), 5-N-acetyl-8-O-methyl-neuraminic acid (Neu5Ac8Me) and the 1,7-lactone (Neu5Ac1,7L) of neuraminic acid. Neu4,5Ac2, relatively abundant in the gut, was present as a minor compound in all tissues, including liver, olfactory lobe, telencephalon, metencephalon and hippocampus. Neu5,9Ac2 was also found in these tissues, except in the liver. It is suggested that these sialic acids represent the endogenous substrate and receptor determinants for murine coronaviruses.

Keywords: Gas chromatography, Mass-spectrometry, Mouse hepatitis virus, Mouse tissues, 5-N-acetyl-4-O-acetylneuraminic acid, Sialic acid

Abbreviations

amu

atomic mass unit

EI

electron impact ionization

GC

gas chromatography

MS

mass-spectrometry

HFB

heptafluorobutyrate

HFBAA

heptafluorobutyricacid anhydride

Kdn

3-deoxy-D-glycero-D-galacto-nonulosonic acid; the nomenclature of the other sialic acids is after Schauer and Kamerling [36]

TIC

total ion count

HE

hemagglutinin esterase

MHV

mouse hepatitis virus

References

  • 1.Enjuanes, L., Brian, D.A., Cavanagh, D., Holmes, K.V., Lai, M.M.C., Laude, H., Masters, P.S., Rottier, P., Siddell, S., Spaan, W., Taguchi, F., Talbot, P.J.: Nidovirales. In: M.H.V. van Regenmortel, C.M. Fauquet, and D.H.L. Bishop (Eds.) Virus Taxonomy. Classification and Nomenclature of Viruses. Seventh report of the International Committee on Taxonomy of Viruses, (Academic Press, San Diego, 2000)
  • 2.Drosten C., Gunther S., Preiser W., Van Der Werf S., Brodt H.R., Becker S., Rabenau H., Panning M., Kolesnikova L., Fouchier R.A., Berger A., Burguiere A.M., Cinatl J., Eickmann M., Escriou N., Grywna K., Kramme S., Manuguerra J.C., Muller S., Rickerts V., Sturmer M., Vieth S., Klenk H.D., Osterhaus A.D., Schmitz H., Doerr H.W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003;10:10. doi: 10.1056/NEJMoa030747. [DOI] [PubMed] [Google Scholar]
  • 3.Ksiazek T.G., Erdman D., Goldsmith C.S., Zaki S.R., Peret T., Emery S., Tong S., Urbani C., Comer J.A., Lim W., Rollin P.E., Dowell S.F., Ling A.E., Humphrey C.D., Shieh W.J., Guarner J., Paddock C.D., Rota P., Fields B., DeRisi J., Yang J.Y., Cox N., Hughes J.M., LeDuc J.W., Bellini W.J., Anderson L.J. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 2003;30:30. doi: 10.1056/NEJMoa030781. [DOI] [PubMed] [Google Scholar]
  • 4.Marra, M.A., Jones, S.J.M., Astell, C.R., Holt, R.A., Brooks-Wilson, A., Butterfield, Y.S.N., Khattra, J., Asano, J.K., Barber, S.A., Chan, S.Y., Cloutier, A., Coughlin, S.M., Freeman, D., Girn, N., Griffith, O.L., Leach, S.R., Mayo, M., McDonald, H., Montgomery, S.B., Pandoh, P.K., Petrescu, A.S., Robertson, A.G., Schein, J.E., Siddiqui, A., Smailus, D.E., Stott, J.M., Yang, G.S., Plummer, F., Andonov, A., Artsob, H., Bastien, N., Bernard, K., Booth, T.F., Bowness, D., Drebot, M., Fernando, L., Flick, R., Garbutt, M., Gray, M., Grolla, A., Jones, S., Feldmann, H., Meyers, A., Kabani, A., Li, Y., Normand, S., Stroher, U., Tipples, G.A., Tyler, S., Vogrig, R., Ward, D., Watson, B., Brunham, R.C., Krajden, M., Petric, M., Skowronski, D.M., Upton, C., Roper, R.L.: The genome sequence of the sars-associated coronavirus. Science 1085953 (2003) [DOI] [PubMed]
  • 5.Rota, P.A., Oberste, M.S., Monroe, S.S., Nix, W.A., Campagnoli, R., Icenogle, J.P., Penaranda, S., Bankamp, B., Maher, K., Chen, M-h., Tong, S., Tamin, A., Lowe, L., Frace, M., DeRisi, J.L., Chen, Q., Wang, D., Erdman, D.D., Peret, T.C.T., Burns, C., Ksiazek, T.G., Rollin, P.E., Sanchez, A., Liffick, S., Holloway, B., Limor, J., McCaustland, K., Olsen-Rassmussen, M., Fouchier, R., Gunther, S., Osterhaus, A.D.M.E., Drosten, C., Pallansch, M.A., Anderson, L.J., Bellini, W.J.: Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 1085952 (2003) [DOI] [PubMed]
  • 6.Snijder E.J., Bredenbeek P.J., Dobbe J.C., Thiel V., Ziebuhr J., Poon L.L., Guan Y., Rozanov M., Spaan W.J., Gorbalenya A.E. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J. Mol. Biol. 2003;331:991–1004. doi: 10.1016/S0022-2836(03)00865-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.van der Hoek L., Pyrc K., Jebbink M.F., Vermeulen-Oost W., Berkhout R.J., Wolthers K.C., Wertheim-van Dillen P.M., Kaandorp J., Spaargaren J., Berkhout B. Identification of a new human coronavirus. Nat. Med. 2004;10:368–73. doi: 10.1038/nm1024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Woo P.C., Lau S.K., Chu C.M., Chan K.H., Tsoi H.W., Huang Y., Wong B.H., Poon R.W., Cai J.J., Luk W.K., Poon L.L., Wong S.S., Guan Y., Peiris J.S., Yuen K.Y. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J. Virol. 2005;79:884–95. doi: 10.1128/JVI.79.2.884-895.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Regl G., Kaser A., Iwersen M., Schmid H., Kohla G., Strobl B., Vilas U., Schauer R., Vlasak R. The hemagglutinin-esterase of mouse hepatitis virus strain S is a sialate-4-O-acetylesterase. J. Virol. 1999;73:4721–7. doi: 10.1128/jvi.73.6.4721-4727.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Klausegger A., Strobl B., Regl G., Kaser A., Luytjes W., Vlasak R. Identification of a coronavirus hemagglutinin-esterase with a substrate specificity different from those of influenza C virus and bovine coronavirus. J. Virol. 1999;73:3737–43. doi: 10.1128/jvi.73.5.3737-3743.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Strasser P., Unger U., Strobl B., Vilas U., Vlasak R. Recombinant viral sialate-O-acetylesterases. Glycoconj. J. 2004;20:551–61. doi: 10.1023/B:GLYC.0000043292.64358.f1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Wurzer W.J., Obojes K., Vlasak R. The sialate-4-O-acetylesterases of coronaviruses related to mouse hepatitis virus: A proposal to reorganize group 2 Coronaviridae. J. Gen. Virol. 2002;83:395–402. doi: 10.1099/0022-1317-83-2-395. [DOI] [PubMed] [Google Scholar]
  • 13.Vlasak R., Luytjes W., Leider J., Spaan W., Palese P. The E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity. J. Virol. 1988;62:4686–90. doi: 10.1128/jvi.62.12.4686-4690.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Vlasak R., Luytjes W., Spaan W. Palese P, Human and bovine coronaviruses recognize sialic acid-containing receptors similar to those of influenza C viruses. Proc. Natl. Acad. Sci. USA. 1988;85:4526–9. doi: 10.1073/pnas.85.12.4526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Schultze B., Gross H.J., Brossmer R., Herrler G. The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant. J. Virol. 1991;65:6232–7. doi: 10.1128/jvi.65.11.6232-6237.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Dveksler G.S., Pensiero M.N., Cardellichio C.B., Williams R.K., Jiang G.S., Holmes K.V., Dieffenbach C.W. Cloning of the mouse hepatitis virus (MHV) receptor: Expression in human and hamster cell lines confers susceptibility to MHV. J. Virol. 1991;65:6881–91. doi: 10.1128/jvi.65.12.6881-6891.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Nedellec P., Dveksler G.S., Daniels E., Turbide C., Chow B., Basile A.A., Holmes K.V., Beauchemin N. Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses. J. Virol. 1994;68:4525–37. doi: 10.1128/jvi.68.7.4525-4537.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Tan K., Zelus B.D., Meijers R., Liu J.H., Bergelson J.M., Duke N., Zhang R., Joachimiak A., Holmes K.V., Wang J.H. Crystal structure of murine sCEACAM1a[1, 4]: a coronavirus receptor in the CEA family. Embo. J. 2002;21:2076–86. doi: 10.1093/emboj/21.9.2076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Williams R.K., Jiang G.S., Holmes K.V. Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins. Proc. Natl. Acad. Sci. USA. 1991;88:5533–6. doi: 10.1073/pnas.88.13.5533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Herrler G., Klenk H.D. The surface receptor is a major determinant of the cell tropism of influenza C virus. Virology. 1987;159:102–8. doi: 10.1016/0042-6822(87)90352-7. [DOI] [PubMed] [Google Scholar]
  • 21.Smits S.L., Gerwig G.J., van Vliet A.L., Lissenberg A., Briza P., Kamerling J.P., Vlasak R., de Groot R.J. Nidovirus Sialate-O-Acetylesterases: Evolution and substrate specificity and substrate specificity of coronaviral and toroviral receptor-destroying enzymes. J. Biol. Chem. 2005;280:6933–41. doi: 10.1074/jbc.M409683200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Iwersen M., Vandamme-Feldhaus V., Schauer R. Enzymatic 4-O-acetylation of N-acetylneuraminic acid in guinea-pig liver. Glycoconj. J. 1998;15:895–904. doi: 10.1023/A:1006911100081. [DOI] [PubMed] [Google Scholar]
  • 23.Schauer R., Schmid H., Pommerencke J., Iwersen M., Kohla G. Metabolism and role of O-acetylated sialic acids. Adv. Exp. Med. Biol. 2001;491:325–42. doi: 10.1007/978-1-4615-1267-7_21. [DOI] [PubMed] [Google Scholar]
  • 24.Morimoto N., Nakano M., Kinoshita M., Kawabata A., Morita M., Oda Y., Kuroda R., Kakehi K. Specific distribution of sialic acids in animal tissues as examined by LC-ESI-MS after derivatization with 1,2-diamino-4,5- methylenedioxybenzene. Anal. Chem. 2001;73:5422–8. doi: 10.1021/ac0104328. [DOI] [PubMed] [Google Scholar]
  • 25.Barthold S.W., Beck D.S., Smith A.L. Mouse hepatitis virus nasoencephalopathy is dependent upon virus strain and host genotype. Arch. Virol. 1986;91:247–56. doi: 10.1007/BF01314284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Taguchi F., Yamada A., Fujiwara K. Asymptomatic infection of mouse hepatitis virus in the rat. Brief report. Arch. Virol. 1979;59:275–9. doi: 10.1007/BF01317424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Lavi E., Gilden D.H., Highkin M.K., Weiss S.R. The organ tropism of mouse hepatitis virus A59 in mice is dependent on dose and route of inoculation. Lab. Anim. Sci. 1986;36:130–5. [PubMed] [Google Scholar]
  • 28.Lavi E., Gilden D.H., Wroblewska Z., Rorke L.B., Weiss S.R. Experimental demyelination produced by the A59 strain of mouse hepatitis virus. Neurology. 1984;34:597–603. doi: 10.1212/wnl.34.5.597. [DOI] [PubMed] [Google Scholar]
  • 29.Homberger F.R. Enterotropic mouse hepatitis virus. Lab. Anim. 1997;31:97–115. doi: 10.1258/002367797780600189. [DOI] [PubMed] [Google Scholar]
  • 30.Zanetta J.P., Pons A., Iwersen M., Mariller C., Leroy Y., Timmerman P., Schauer R. Diversity of sialic acids revealed using gas chromatography/mass spectrometry of heptafluorobutyrate derivatives. Glycobiology. 2001;11:663–76. doi: 10.1093/glycob/11.8.663. [DOI] [PubMed] [Google Scholar]
  • 31.Bulai T., Bratosin D., Pons A., Montreuil J., Zanetta J.P. Diversity of the human erythrocyte membrane sialic acids in relation with blood groups. FEBS Lett. 2003;534:185–9. doi: 10.1016/S0014-5793(02)03838-3. [DOI] [PubMed] [Google Scholar]
  • 32.Robbe C., Capon C., Maes E., Rousset M., Zweibaum A., Zanetta J.P., Michalski J.C. Evidence of regio-specific glycosylation in human intestinal mucins: Presence of an acidic gradient along the intestinal tract. J. Biol. Chem. 2003;278:46337–48. doi: 10.1074/jbc.M302529200. [DOI] [PubMed] [Google Scholar]
  • 33.Bauer H.C., Tontsch U. Glial-conditioned medium and attachment to ConA are essential for long- term culture of cortical neurons. Int. J. Dev. Neurosci. 1990;8:151–8. doi: 10.1016/0736-5748(90)90005-m. [DOI] [PubMed] [Google Scholar]
  • 34.Sjoberg E.R., Chammas R., Ozawa H., Kawashima I., Khoo K-H., Morris H.R., Dell A., Tai T., Varki A. Expression of De-N-acetyl-gangliosides in Human Melanoma Cells Is Induced by Genistein or Nocodazole. J. Biol. Chem. 1995;270:2921–30. doi: 10.1074/jbc.270.7.2921. [DOI] [PubMed] [Google Scholar]
  • 35.Kamerling J.P., Vliegenthart J.F.G., Versluis C., Schauer R. Identification of O-acetylated N-acylneuraminic acids by mass spectrometry. Carbohydr Res. 1975;41:7–17. doi: 10.1016/S0008-6215(00)87002-0. [DOI] [PubMed] [Google Scholar]
  • 36.Schauer, R., Kamerling, J.P.: Chemistry, biochemistry and biology of sialic acids, In: J. Montreuil, J.F.G. Vliegenthart, H. Schachter Glycoproteins II, (Elsevier, Amsterdam, 1997) pp. 243–402
  • 37.Hara S., Yamaguchi M., Takemori Y., Furuhata K., Ogura H., Nakamura M. Determination of mono-O-acetylated N-acetylneuraminic acids in human and rat sera by fluorometric high-performance liquid chromatography. Anal. Biochem. 1989;179:162–6. doi: 10.1016/0003-2697(89)90218-2. [DOI] [PubMed] [Google Scholar]
  • 38.Klein A., Diaz S., Ferreira I., Lamblin G., Roussel P., Manzi A.E. New sialic acids from biological sources identified by a comprehensive and sensitive approach: Liquid chromatography-electrospray ionization- mass spectrometry (LC-ESI-MS) of SIA quinoxalinones. Glycobiology. 1997;7:421–32. doi: 10.1093/glycob/7.3.421. [DOI] [PubMed] [Google Scholar]
  • 39.Kohla G., Stockfleth E., Schauer R. Gangliosides with O-acetylated sialic acids in tumors of neuroectocermal origin. Neurochem Res. 2002;27:583–92. doi: 10.1023/A:1020211714104. [DOI] [PubMed] [Google Scholar]
  • 40.Reuter G., Schauer R. Comparison of electron and chemical ionization mass spectrometry of sialic acids. Anal. Biochem. 1986;157:39–46. doi: 10.1016/0003-2697(86)90193-4. [DOI] [PubMed] [Google Scholar]
  • 41.Sonnino S., Ghidoni R., Chigorno V., Masserini M., Tettamanti G. Recognition by two-dimensional thin-layer chromatography and densitometric quantification of alkali-labile gangliosides from the brain of different animals. Anal. Biochem. 1983;128:104–14. doi: 10.1016/0003-2697(83)90350-0. [DOI] [PubMed] [Google Scholar]
  • 42.Zhang G., Kurono S., Fujita S.C., Furuya S., Hirabashi Y. Developmentally regulated O-acetylated sialoglycans in the central nervous system revealed by a new monoclonal antibody 493D4 recognizing a wide range of O-acetylated glycoconjugates. Glycobiology. 1997;14:847–57. doi: 10.1023/A:1018542105832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Shi W.X., Chammas R., Varki A. Regulation of sialic acid 9-O-acetylation during the growth and differentiation of murine erythroleukemia cells. J. Biol. Chem. 1996;271:31517–25. doi: 10.1074/jbc.271.49.31517. [DOI] [PubMed] [Google Scholar]
  • 44.Tiralongo J., Schmid H., Thun R., Iwersen M., Schauer R. Characterisation of the enzymatic 4-O-acetylation of sialic acids in microsomes from equine submandibular glands. Glycoconj. J. 2000;17:849–58. doi: 10.1023/A:1010965128335. [DOI] [PubMed] [Google Scholar]
  • 45.Iwersen M., Dora H., Kohla G., Gasa S., Schauer R. Solubilisation and properties of the sialate-4-O-acetyltransferase from guinea pig liver. Biol Chem. 2003;384:1035–47. doi: 10.1515/BC.2003.116. [DOI] [PubMed] [Google Scholar]
  • 46.Chou H.H., Hayakawa T., Diaz S., Krings M., Indriati E., Leakey M., Paabo S., Satta Y., Takahata N., Varki A. Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution. Proc. Natl. Acad. Sci. USA. 2002;99:11736–41. doi: 10.1073/pnas.182257399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Kelm S., Schauer R. Sialic acids in molecular and cellular interactions. Int. Rev. Cytol. 1997;175:137–240. doi: 10.1016/S0074-7696(08)62127-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Chammas R., Sonnenburg J.L., Watson N.E., Tai T., Farquhar M.G., Varki N.M., Varki A. De-N-acetyl-gangliosides in humans: unusual subcellular distribution of a novel tumor antigen. Cancer. Res. 1999;59:1337–46. [PubMed] [Google Scholar]
  • 49.Zhou Q., Hakomori S., Kitamura K., Igarashi Y. GM3 directly inhibits tyrosine phosphorylation and de-N-acetyl-GM3 directly enhances serine phosphorylation of epidermal growth factor receptor, independently of receptor-receptor interaction. J. Biol. Chem. 1994;269:1959–65. [PubMed] [Google Scholar]
  • 50.Manzi A.E., Sjoberg E.R., Diaz S., Varki A. Biosynthesis and turnover of O-acetyl and N-acetyl groups in the gangliosides of human melanoma cells. J. Biol. Chem. 1990;265:13091–103. [PubMed] [Google Scholar]
  • 51.Cebo C., Dambrouck T., Maes E., Laden C., Strecker G., Michalski J.C., Zanetta J.P. Recombinant human interleukins IL-1alpha, IL-1beta, IL-4, IL-6, and IL-7 show different and specific calcium-independent carbohydrate-binding properties. J. Biol. Chem. 2001;276:5685–91. doi: 10.1074/jbc.M008662200. [DOI] [PubMed] [Google Scholar]
  • 52.Barnett E.M., Cassell M.D., Perlman S. Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus, spread along different neural pathways from the main olfactory bulb. Neuroscience. 1993;57:1007–25. doi: 10.1016/0306-4522(93)90045-H. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Hemmila E., Turbide C., Olson M., Jothy S., Holmes K.V., Beauchemin N. Ceacam1a−/− mice are completely resistant to infection by murine coronavirus mouse hepatitis virus A59. J. Virol. 2004;78:10156–65. doi: 10.1128/JVI.78.18.10156-10165.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Muchova L., Jirsa M., Kuroki M., Dudkova L., Benes M.J., Marecek Z., Smid F. Immunoaffinity isolation of CEACAM1 on hydrazide-derivatized cellulose with immobilized monoclonal anti-CEA antibody. Biomed Chromatogr. 2001;15:418–22. doi: 10.1002/bmc.92. [DOI] [PubMed] [Google Scholar]
  • 55.Lewicki D.N., Gallagher T.M. Quaternary structure of coronavirus spikes in complex with carcinoembryonic antigen-related cell adhesion molecule cellular receptors. J. Biol. Chem. 2002;277:19727–34. doi: 10.1074/jbc.M201837200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Markovic I., Clouse K.A. Recent advances in understanding the molecular mechanisms of HIV-1 entry and fusion: revisiting current targets and considering new options for therapeutic intervention. Curr HIV Res. 2004;2:223–34. doi: 10.2174/1570162043351327. [DOI] [PubMed] [Google Scholar]
  • 57.Oppermann M. Chemokine receptor CCR5: insights into structure, function, and regulation. Cell Signal. 2004;16:1201–10. doi: 10.1016/j.cellsig.2004.04.007. [DOI] [PubMed] [Google Scholar]
  • 58.Philpott S.M. HIV-1 coreceptor usage, transmission, and disease progression. Curr. HIV Res. 2003;1:217–27. doi: 10.2174/1570162033485357. [DOI] [PubMed] [Google Scholar]

Articles from Glycoconjugate Journal are provided here courtesy of Nature Publishing Group

RESOURCES