Nuclear export of the nonenveloped parvovirus virion is directed by an unordered protein signal exposed on the capsid surface.
It is uncertain whether nonenveloped karyophilic virus particles may actively traffic from the nucleus outward. The unordered amino-terminal domain of the VP2 major structural protein (2Nt) of the icosahedral parvovirus minute virus of mice (MVM) is internal in empty capsids, but it is exposed outside of the shell through the fivefold axis of symmetry in virions with an encapsidated single-stranded DNA genome, as well as in empty capsids subjected to a heat-induced structural transition. In productive infections of transformed and normal fibroblasts, mature MVM virions were found to efficiently exit from the nucleus prior to cell lysis, in contrast to the extended nuclear accumulation of empty capsids. Newly formed mutant viruses lacking the three phosphorylated serine residues of 2Nt were hampered in their exit from the human transformed NB324K nucleus, in correspondence with the capacity of 2Nt to drive microinjected phosphorylated heated capsids out of the nucleus. However, in normal mouse A9 fibroblasts, in which the MVM capsid was phosphorylated at similar sites but with a much lower rate, the nuclear exit of virions and microinjected capsids harboring exposed 2Nt required the infection process and was highly sensitive to inhibition of the exportin CRM1 in the absence of a demonstrable interaction. Thus, the MVM virion exits the nucleus by accessing nonconventional export pathways relying on cell physiology that can be intensified by infection but in which the exposure of 2Nt remains essential for transport. The flexible 2Nt nuclear transport signal may illustrate a common structural solution used by nonenveloped spherical viruses to propagate in undamaged host tissues.
Maroto
Beatriz
B
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Valle
Noelia
N
Saffrich
Rainer
R
Almendral
José M
JM
D021581:Active Transport, Cell Nucleus; D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology*; D002472:Cell Transformation, Viral; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D051379:Mice; D008915:Minute Virus of Mice / Q000254:growth & development / Q000378:metabolism*; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear; D014771:Virion / Q000378:metabolism; D000097606:Exportin 1 Protein
D036022:Capsid Proteins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein