Journal of General Virology, Vol 78, 2041-2048, Copyright © 1997 by Society for General Microbiology

ARTICLES

Antibodies against vaccinia virus do not neutralize extracellular enveloped virus but prevent virus release from infected cells and comet formation

A Vanderplasschen, M Hollinshead and GL Smith
Sir William Dunn School of Pathology, University of Oxford, UK.

Vaccinia virus (VV) produces two antigenically and structurally distinct infectious virions, intracellular mature virus (IMV) and extracellular enveloped virus (EEV). EEV is important for the efficient dissemination of virus both in vivo and in vitro where it causes formation of comet-shaped virus plaques. Here, we show that EEV, in contrast to IMV, is resistant to neutralization by antibodies bound to its surface. However, antibodies against EEV can prevent comet formation in cell culture. To explain this apparent paradox, we investigated the mechanism by which antibodies inhibit comet formation and demonstrated that antibodies prevent EEV release from infected cells, and consequently comet formation, by agglutination of the virus on the cell surface. Two complementary observations allow this conclusion: first, electron microscopy showed that infected cells incubated with medium containing anti-vaccinia virus antibodies have virus aggregates on their surface; second, culture medium from these cells contained a 4 log10 fold reduction in the physical particle/ml titre in comparison with control culture. A mechanism by which antibodies to EEV proteins provide immunological protection is thus restriction of EEV release rather than neutralization of free EEV particles.

This article has been cited by other articles:

				C.-Y. Huang, T.-Y. Lu, C.-H. Bair, Y.-S. Chang, J.-K. Jwo, and W. Chang A Novel Cellular Protein, VPEF, Facilitates Vaccinia Virus Penetration into HeLa Cells through Fluid Phase Endocytosis J. Virol., August 15, 2008; 82(16): 7988 - 7999. [Abstract] [Full Text] [PDF]

				A. Berhanu, R. L. Wilson, D. L. Kirkwood-Watts, D. S. King, T. K. Warren, S. A. Lund, L. L. Brown, A. K. Krupkin, E. VanderMay, W. Weimers, et al. Vaccination of BALB/c Mice with Escherichia coli-Expressed Vaccinia Virus Proteins A27L, B5R, and D8L Protects Mice from Lethal Vaccinia Virus Challenge J. Virol., April 1, 2008; 82(7): 3517 - 3529. [Abstract] [Full Text] [PDF]

				L. Aldaz-Carroll, Y. Xiao, J. C. Whitbeck, M. P. de Leon, H. Lou, M. Kim, J. Yu, E. L. Reinherz, S. N. Isaacs, R. J. Eisenberg, et al. Major Neutralizing Sites on Vaccinia Virus Glycoprotein B5 Are Exposed Differently on Variola Virus Ortholog B6 J. Virol., August 1, 2007; 81(15): 8131 - 8139. [Abstract] [Full Text] [PDF]

				A. D. Garcia, C. A. Meseda, A. E. Mayer, A. Kumar, M. Merchlinsky, and J. P. Weir Characterization and Use of Mammalian-Expressed Vaccinia Virus Extracellular Membrane Proteins for Quantification of the Humoral Immune Response to Smallpox Vaccines Clin. Vaccine Immunol., August 1, 2007; 14(8): 1032 - 1044. [Abstract] [Full Text] [PDF]

				M. M. Putz, I. Alberini, C. M. Midgley, I. Manini, E. Montomoli, and G. L. Smith Prevalence of antibodies to Vaccinia virus after smallpox vaccination in Italy J. Gen. Virol., November 1, 2005; 86(11): 2955 - 2960. [Abstract] [Full Text] [PDF]

				L. Aldaz-Carroll, J. C. Whitbeck, M. Ponce de Leon, H. Lou, L. Hirao, S. N. Isaacs, B. Moss, R. J. Eisenberg, and G. H. Cohen Epitope-Mapping Studies Define Two Major Neutralization Sites on the Vaccinia Virus Extracellular Enveloped Virus Glycoprotein B5R J. Virol., May 15, 2005; 79(10): 6260 - 6271. [Abstract] [Full Text] [PDF]

				C. Fogg, S. Lustig, J. C. Whitbeck, R. J. Eisenberg, G. H. Cohen, and B. Moss Protective Immunity to Vaccinia Virus Induced by Vaccination with Multiple Recombinant Outer Membrane Proteins of Intracellular and Extracellular Virions J. Virol., October 1, 2004; 78(19): 10230 - 10237. [Abstract] [Full Text] [PDF]

				G. L. Smith, A. Vanderplasschen, and M. Law The formation and function of extracellular enveloped vaccinia virus J. Gen. Virol., December 1, 2002; 83(12): 2915 - 2931. [Abstract] [Full Text] [PDF]

				O. Krauss, R. Hollinshead, M. Hollinshead, and G. L. Smith An investigation of incorporation of cellular antigens into vaccinia virus particles J. Gen. Virol., October 1, 2002; 83(10): 2347 - 2359. [Abstract] [Full Text] [PDF]

				J. C. Ramirez, E. Tapia, and M. Esteban Administration to mice of a monoclonal antibody that neutralizes the intracellular mature virus form of vaccinia virus limits virus replication efficiently under prophylactic and therapeutic conditions J. Gen. Virol., May 1, 2002; 83(5): 1059 - 1067. [Abstract] [Full Text] [PDF]

				M. Law, R. Hollinshead, and G. L. Smith Antibody-sensitive and antibody-resistant cell-to-cell spread by vaccinia virus: role of the A33R protein in antibody-resistant spread J. Gen. Virol., January 1, 2002; 83(1): 209 - 222. [Abstract] [Full Text] [PDF]

				A. Vanderplasschen, E. Mathew, M. Hollinshead, R. B. Sim, and G. L. Smith Extracellular enveloped vaccinia virus is resistant to complement because of incorporation of host complement control proteins into its envelope PNAS, June 23, 1998; 95(13): 7544 - 7549. [Abstract] [Full Text] [PDF]

				E. Mathew, C. M. Sanderson, M. Hollinshead, and G. L. Smith The Extracellular Domain of Vaccinia Virus Protein B5R Affects Plaque Phenotype, Extracellular Enveloped Virus Release, and Intracellular Actin Tail Formation J. Virol., March 1, 1998; 72(3): 2429 - 2438. [Abstract] [Full Text] [PDF]