Friday, 18 November 2011 09:45

Infection Path of Measles virus identified in vitro Featured

Led by Dr. Michael Mühlebach, and in cooperation with international research groups from the USA, Canada, Singapore and France, researchers from the medical biotechnology department at the Paul-Ehrlich Institute have shed light on how measles viruses penetrate epithelial cells, from where they are expelled via the respiratory tract and infect other humans.

Several years ago scientists already discovered that measles viruses do not multiply in the epithelial cell layer lining the bronchi, but rather are introduced by immune cells to the lymph nodes and other organs of the lymphatic system. It is there that considerable virus multiplication then takes place. Now it is possible to answer the question as to which path the pathogens take back to the respiratory tract, from where they can then be transported outside the body.

The scientists were looking for a protein seated on the inner side of the epithel cell layer, which would accessible to the viruses and enable them to pass through the epithelial cells. The researchers used seven different cell lines from pulmonary and cystic tumours. One part of the cell lines was able to be infected by measles viruses, the other part was not. The researchers investigated which proteins were formed by the infected group of cell lines but not by the other group. This way, they identified a transmembrane protein called Nectin-4 potentially responsible for infections with measles viruses. In order to prove this, Mühlebach and his colleagues blocked the genetic expression of Nectin-4 in infected cell lines, thus inhibiting viral penetration of the cells.

The results of Mühlebach and his colleagues could be meaningful for cancer therapies, as measles viruses are already used in cancer therapy as oncolytic viruses.

Original publication:
Mühlebach MD, Mateo M, Sinn PL, Prüfer S, Uhlig KM, Leonard VHJ, Navaratnarajah CK, Frenzke M, Wong XX, Sawatsky B, Ramachandran S, McCray Jr PB, Cichutek K, von Messling V, Lopez M, Cattaneo R (2011): Adherens junction protein nectin-4 (PVRL4) is the epithelial receptor for measles virus.

Nature [Epub ahead of print]. DOI: 10.1038/nature10639


Also: Identification of Nectin-4 Oncoprotein as a Diagnostic and Therapeutic Target for Lung Cancer