Glycoprotein targeting signals influence the distribution of measles virus envelope proteins and virus spread in lymphocytes.
We previously demonstrated the presence of tyrosine-dependent motifs for specific sorting of two measles virus (MV) glycoproteins, H and F, to the basolateral surface in polarized epithelial cells. Targeted expression of the glycoproteins was found to be required for virus spread in epithelia via cell-to-cell fusion in vitro and in vivo. In the present study, recombinant MVs (rMVs) with substitutions of the critical tyrosines in the H and F cytoplasmic domains were used to determine whether the sorting signals also play a crucial role for MV replication and spread within lymphocytes, the main target cells of acute MV infection. Immunolocalization revealed that only standard glycoproteins are targeted specifically to the uropod of polarized lymphocytes and cluster on the surface of non-polarized lymphocytes. H and F proteins with tyrosine mutations did not accumulate in uropods, but were distributed homogeneously on the surface and did not colocalize markedly with the matrix (M) protein. Due to the defective interaction with the M protein, all mutant rMVs showed an enhanced fusion capacity, but only rMVs harbouring two mutated glycoproteins showed a marked decrease in virus release from infected lymphocytes. These results demonstrate clearly that the tyrosine-based targeting motifs in the MV glycoproteins are not only important in polarized epithelial cells, but are also active in lymphocytes, thus playing an important role in virus propagation in different key target cells during acute MV infection.
Runkler
Nicole
N
Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany.
Dietzel
Erik
E
Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany.
Moll
Markus
M
Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany.
Klenk
Hans-Dieter
HD
Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany.
Maisner
Andrea
A
Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany.
D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D016764:Cell Polarity; D002522:Chlorocebus aethiops; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000821:virology*; D008459:Measles virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D009154:Mutation; D021382:Protein Sorting Signals / Q000235:genetics* / Q000502:physiology; D014443:Tyrosine / Q000235:genetics; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
D006389:Hemagglutinins, Viral; D021382:Protein Sorting Signals; D014760:Viral Fusion Proteins; C032397:hemagglutinin protein G, measles virus; D014443:Tyrosine