Expression of measles virus V protein is associated with pathogenicity and control of viral RNA synthesis.

in Journal of virology by C Tober, M Seufert, H Schneider, M A Billeter, I C Johnston, S Niewiesk, V ter Meulen, S Schneider-Schaulies

TLDR

  • The study looked at a protein called V that is made by a virus called measles. The researchers found that V protein helps to balance the amount of other proteins and RNA made by the virus in cells. They also found that V protein interacts with another protein called N, which is important for the virus to make more copies of itself. The study suggests that V protein plays a role in making the virus more harmful to cells and animals.

Abstract

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.

Overview

  • The study focuses on the role of the V protein encoded by measles virus (MV) in viral propagation and pathogenesis. The hypothesis being tested is whether V protein is dispensable for MV propagation in cell culture and whether it contributes to viral pathogenicity in vivo. The methodology used involves the use of recombinant MVs (strain Edmonston [ED]) genetically engineered to overexpress V protein (ED-V+) or to be deficient for V protein (ED-V-). The study aims to determine the impact of V protein on MV-specific protein and RNA accumulation, gene expression, and viral titers in cell culture and in vivo in cotton rats. The primary objective of the study is to understand the role of V protein in MV pathogenesis and to identify potential targets for antiviral therapy.

Comparative Analysis & Findings

  • The study found that in the absence of V protein, MV-specific proteins and RNAs accumulated to higher levels than those in the parental MV molecular clone (ED-tag), whereas MV-specific gene expression was strongly attenuated. The titers of virus released from cells infected 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 after intranasal infection with both editing mutants compared to titers isolated from ED-tag-infected animals. These findings suggest that V protein plays a role in regulating the accumulation of viral gene products in cell culture and in vivo, and that its interaction with MV N protein may be critical for viral pathogenesis.

Implications and Future Directions

  • The study's findings have important implications for the development of antiviral therapies targeting V protein. The study also highlights the importance of understanding the role of nonstructural proteins in viral pathogenesis and the potential for these proteins to be targeted for therapeutic intervention. Future research could focus on identifying specific domains of V protein that interact with MV N protein and on developing small molecule inhibitors of these interactions. Additionally, further studies could investigate the role of V protein in MV-induced immune suppression and its potential as a target for immunotherapies.
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