Antibody-sensitive and antibody-resistant cell-to-cell spread by vaccinia virus: role of the A33R protein in antibody-resistant spread.
The roles of vaccinia virus (VV) intracellular mature virus (IMV), intracellular enveloped virus (IEV), cell-associated enveloped virus (CEV) and extracellular enveloped virus (EEV) and their associated proteins in virus spread were investigated. The plaques made by VV mutants lacking individual IEV- or EEV-specific proteins (vDeltaA33R, vDeltaA34R, vDeltaA36R, vDeltaA56R, vDeltaB5R, vDeltaF12L and vDeltaF13L) were compared in the presence of IMV- or EEV-neutralizing antibodies (Ab). Data presented show that for long-range spread, the comet-shaped plaques of VV were caused by the unidirectional spread of EEV probably by convection currents, and for cell-to-cell spread, VV uses a combination of Ab-resistant and Ab-sensitive pathways. Actin tails play a major role in the Ab-resistant pathway, but mutants such as vDeltaA34R and vDeltaA36R that do not make actin tails still spread from cell to cell in the presence of Ab. Most strikingly, the Ab-resistant pathway was abolished when the A33R gene was deleted. This effect was not due to alterations in the efficiency of neutralization of EEV made by this mutant, nor due to a deficiency in IMV wrapping to form IEV, which was indispensable for EEV formation by vDeltaA33R and vDeltaA34R. We suggest a role for A33R in promoting Ab-resistant cell-to-cell spread of virus. The roles of the different virus forms in the VV life-cycle are discussed.
Law
Mansun
M
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
Hollinshead
Ruth
R
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
Smith
Geoffrey L
GL
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D014616:Vaccinia virus / Q000276:immunology / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019065:Virus Assembly / Q000502:physiology*
C446940:A33R protein, Vaccinia virus; D000914:Antibodies, Viral; C087715:L1R protein, Vaccinia virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C074512:42kDa protein, Vaccinia virus