Multiple vesiculoviral matrix proteins inhibit both nuclear export and import

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• The matrix (M) protein of vesicular stomatitis virus (VSV) is known to interfere with nuclear transport.
• Understanding the broader role of M proteins in vesiculovirus infection is crucial for comprehending viral pathogenesis.

Purpose of the Study:

• To investigate the conservation of nuclear transport inhibitory properties among matrix (M) proteins of different vesiculoviruses.
• To elucidate the mechanism by which M proteins affect nuclear transport.

Main Methods:

• Comparative analysis of M proteins from VSV, chandipura virus, and spring viremia carp virus.
• Expression of M proteins in transfected HeLa cells and assessment of their impact on nuclear transport of various cargoes (mRNA, snRNAs, snRNPs).
• Site-directed mutagenesis to identify key residues involved in M protein function and localization.

Main Results:

• M proteins from all three tested vesiculoviruses inhibit nuclear import and export, particularly blocking transport of spliced mRNA, small nuclear RNAs, and small nuclear ribonucleoproteins.
• Chandipura virus M protein exhibited the strongest inhibitory activity among those that only slowed transport.
• Active M proteins localized to the nuclear rim, and mutation of a conserved methionine residue abolished both inhibitory activity and nuclear rim targeting.

Conclusions:

• The nuclear transport inhibitory function of the matrix (M) protein is conserved across vesiculoviruses.
• Vesiculoviral M proteins likely interact with a common nuclear target, potentially a component of the nuclear pore complex, to exert their inhibitory effects.
• The nuclear rim localization and conserved methionine residue are critical for M protein-mediated inhibition of nuclear transport.