Sub-Projects of SFB 535
Invasion and Replication Strategies of Pathogenes
<< back  
SFB Homepage Organisation / Contact Members Announcements
Research Program Sub-Projects Publications Current
Workbench Public Seminars Internal Seminars Search
SP A17

Importance of envelope protein interactions for cell-to-cell spread and release of measles virus



HD Dr. Andrea Maisner
Insitut für Virologie, Philipps-Universität Marburg

Summary

Measles virus (MV) has a negative-stranded RNA genome and consists of only six structural proteins. Three of them (N, P, and L) encapsidate the viral RNA and form the nucleocapsid, three (H, F and M) are associated with the lipid envelope. Whereas the two surface glycoproteins H and F are inserted into the membrane and are responsible for receptor binding and membrane fusion, the matrix protein (M) is associated with the inner side of the lipid envelope and mediates the contact between the glycoproteins and the viral nucleocapsids.
MV has developed a replication strategy that enables the virus to establish an acute systemic infection which still causes about 1 million deaths per year. In contrast to many other human viruses, MV replication in vivo and in cell culture is characterized by a very inefficient virus release from the infected cells and a rapid spread via cell-to-cell fusion. For a productive MV infection, virus distribution directly from cell to cell is obviously more important than virus release. The poor production of cell-free virions in vivo is possibly an important strategy to facilitate escape from the humoral antiviral immune response. The way of virus spread clearly determines the course of a MV infection in vitro and in vivo. Since the efficiency of virus release and cell-to-cell fusion is regulated by interactions between the MV envelope proteins within infected cells, with the M protein as key player, the aim of this project is to analyze the molecular interactions between the M protein and the glycoproteins on one hand and the nucleocapsids on the other hand by using recombinant MV with targeted mutations within the envelope proteins. Following questions should be answered.

Part A (Interactions of the envelope proteins M, H and F):
What is the role of the cytoplasmic tails and the transmembrane domains of the viral glycoproteins H and F for M-protein binding, and how do changes in these domains influence cell-to-cell fusion, quantitative virus release, protein composition of cell-free virions and their ability to infect new host cells.

Part B (Interactions of M protein and nucleocapsids):
What is the role of M binding to nucleocapsids for the transport to the plasma membrane, and how does M-nucleocapsid binding influence the postulated M-mediated transcription inhibition, i.e. virus replication.

>> Publications
 
SFB Homepage Organisation / Contact Members Announcements
Research Program Sub-Projects Publications Current
Workbench Public Seminars Internal Seminars Search
<< back | ^ Top of Page