Measles virus spread by cell-cell contacts: uncoupling of contact-mediated receptor (CD46) downregulation from virus uptake.
CD46, which serves as a receptor for measles virus (MV; strain Edmonston), is rapidly downregulated from the cell surface after contact with viral particles or infected cells. We show here that the same two CD46 complement control protein (CCP) domains responsible for primary MV attachment mediate its downregulation. Optimal downregulation efficiency was obtained with CD46 recombinants containing CCP domains 1 and 2, whereas CCP 1, alone and duplicated, induced a slight downregulation. Using persistently infected monocytic/promyelocytic U937 cells which release very small amounts of infectious virus, and uninfected HeLa cells as contact partners, we then showed that during contact the formation of CD46-containing patches and caps precedes CD46 internalization. Nevertheless, neither substances inhibiting capping nor the fusion-inhibiting peptide Z-D-Phe-L-Phe-Gly-OH (FIP) blocked CD46 downregulation. Thus, CD46 downregulation can be uncoupled from fusion and subsequent virus uptake. Interestingly, in that system cell-cell contacts lead to a remarkably efficient infection of the target cells which is only partially inhibited by FIP. The finding that the contact of an infected with uninfected cells results in transfer of infectious viral material without significant (complete) fusion of the donor with the recipient cell suggests that microfusion events and/or FIP-independent mechanisms may mediate the transfer of MV infectivity from cell to cell.
Firsching
R
R
Institut für Virologie und Immunbiologie, D-97078 Würzburg, Germany.
Buchholz
C J
CJ
Schneider
U
U
Cattaneo
R
R
ter Meulen
V
V
Schneider-Schaulies
J
J
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002450:Cell Communication; D006224:Cricetinae; D015536:Down-Regulation; D006367:HeLa Cells; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006801:Humans; D008459:Measles virus / Q000378:metabolism* / Q000502:physiology; D051916:Membrane Cofactor Protein; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D014764:Viral Proteins / Q000378:metabolism; D017735:Virus Latency
D015703:Antigens, CD; C497857:CD46 protein, human; D006389:Hemagglutinins, Viral; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D011991:Receptors, Virus; D014764:Viral Proteins; C032397:hemagglutinin protein G, measles virus; C058314:nucleoprotein, Measles virus