Measles virus spread by cell-cell contacts: Uncoupling of contact-mediatedreceptor (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 par ticles or infected cells. We show here that the same two CD46 complement co ntrol protein (CCP) domains responsible for primary MV attachment mediate i ts downregulation. Optimal downregulation efficiency was obtained with CD46 recombinants containing CCP domains 1 and 2, whereas CCP 1, alone and dupl icated, induced a slight downregulation, Using persistently infected monocy tic/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 C D46 internalization. Nevertheless, neither substances inhibiting capping no r the fusion-inhibiting peptide Z-D-Phe-L-Phe-Gly-OH (FIP) blocked CD46 dow nregulation. Thus, CD46 downregulation can be uncoupled from fusion and sub sequent virus uptake. Interestingly, in that system cell-cell contacts lead to a remarkably efficient infection of the target cells which is only part ially inhibited by FIP. The finding that the contact of an infected with un infected cells results in transfer of infectious viral material without sig nificant (complete) fusion of the donor with the recipient cell suggests th at microfusion events and/or FIP-independent mechanisms may mediate the tra nsfer of MV infectivity from cell to cell.