Minute virus of mice NS1 interacts with the SMN protein, and they colocalize in novel nuclear bodies induced by parvovirus infection.
The human survival motor neuron (SMN) gene is the spinal muscular atrophy-determining gene, and a knockout of the murine Smn gene results in preembryonic lethality. Here we show that SMN can directly interact in vitro and in vivo with the large nonstructural protein NS1 of the autonomous parvovirus minute virus of mice (MVM), a protein essential for viral replication and a potent transcriptional activator. Typically, SMN localizes within nuclear Cajal bodies and diffusely in the cytoplasm. Following transient NS1expression, SMN and NS1 colocalize within Cajal bodies. At early time points following parvovirus infection, NS1 fails to colocalize with SMN within Cajal bodies; however, during the course of MVM infection, dramatic nuclear alterations occur. Formerly distinct nuclear bodies such as Cajal bodies, promyelocytic leukemia gene product (PML) oncogenic domains (PODs), speckles, and autonomous parvovirus-associated replication (APAR) bodies are seen aggregating at later points in infection. These newly formed large nuclear bodies (termed SMN-associated APAR bodies) are active sites of viral replication and viral capsid assembly. These results highlight the transient nature of nuclear bodies and their contents and identify a novel nuclear body formed during infection. Furthermore, simple transient expression of the viral nonstructural proteins is insufficient to induce this nuclear reorganization, suggesting that this event is induced specifically by a step in the viral infection process.
Young
Philip J
PJ
Department of Biology, Arizona State University, Tempe, Arizona 85287, USA.
Jensen
Klaus T
KT
Burger
Lisa R
LR
Pintel
David J
DJ
Lorson
Christian L
CL
D000818:Animals; D015374:Biosensing Techniques; D002460:Cell Line; D020541:Coiled Bodies / Q000378:metabolism* / Q000821:virology; D017362:Cyclic AMP Response Element-Binding Protein; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008915:Minute Virus of Mice / Q000472:pathogenicity*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010322:Parvoviridae Infections / Q000821:virology*; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; C081367:NS1 protein, minute virus of mice; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017361:Viral Nonstructural Proteins