Expression of measles virus V protein is associated with pathogenicity and control of viral RNA synthesis.
Nonstructural proteins encoded by measles virus (MV) include the V protein which is translated from an edited P mRNA. V protein is not associated with intracellular or released viral particles and has recently been found to be dispensable for MV propagation in cell culture (H. Schneider, K. Kaelin, and M. A. Billeter, Virology 227:314-322, 1997). Using recombinant MVs (strain Edmonston [ED]) genetically engineered to overexpress V protein (ED-V+) or to be deficient for V protein (ED-V-), we found that in the absence of V both MV-specific proteins and RNAs accumulated to levels higher than those in the parental MV molecular clone (ED-tag), whereas MV-specific gene expression was strongly attenuated in human U-87 glioblastomas cells after infection with ED-V+. The titers of virus released from these cells 48 h after infection with either V mutant virus were lower than those from cells infected with ED-tag. Similarly, significantly reduced titers of infectious virus were reisolated from lung tissue of cotton rats (Sigmodon hispidus) after intranasal infection with both editing mutants compared to titers isolated from ED-tag-infected animals. In cell culture, expression of V protein led to a redistribution of MV N protein in doubly transfected Cos-7 cells, indicating that these proteins form heterologous complexes. This interaction was further confirmed by using a two-hybrid approach with both proteins expressed as Gal4 or VP16 fusion products. Moreover, V protein efficiently competed complexes formed between MV N and P proteins. These findings indicate that V protein acts to balance accumulation of viral gene products in cell culture, and this may be dependent on its interaction with MV N protein. Furthermore, expression of V protein may contribute to viral pathogenicity in vivo.
Tober
C
C
Institute for Virology and Immunobiology, University of Würzburg, D-97078 Würzburg, Germany.
Seufert
M
M
Schneider
H
H
Billeter
M A
MA
Johnston
I C
IC
Niewiesk
S
S
ter Meulen
V
V
Schneider-Schaulies
S
S
D000818:Animals; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000472:pathogenicity*; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics*
D010750:Phosphoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; C069181:V protein, measles virus; D014764:Viral Proteins