The 3' untranslated region of the B19 parvovirus capsid protein mRNAs inhibits its own mRNA translation in nonpermissive cells.
Although parvoviruses are found throughout the animal kingdom, only the human pathogenic B19 virus has so far been shown to possess a limited host range, with erythroid progenitor cells as the main target cells supporting B19 propagation. The underlying mechanism of such erythroid tropism is still unexplained. Synthesis of the NS1 nonstructural protein occurs in permissive and nonpermissive cells, such as megakaryocytes, whereas synthesis of the VP1 and VP2 capsid proteins seems to be restricted to burst-forming units and CFU of erythroid cells. In nonpermissive cells, the NS1 protein is overexpressed and the NS1 RNAs are the predominant RNA species. However, the VP1 and VP2 proteins are not detectable, although the corresponding mRNAs are synthesized. Since all transcripts have part of the 5' untranslated region (5' UTR) in common but distinct 3' UTRs characterizing the nonstructural- and structural-protein mRNAs, we investigated, in transient transfection assays, the possible involvement of the 3' UTR of the capsid protein mRNAs in VP1 and VP2 protein synthesis in nonpermissive Cos cells. The results showed that (i) the 3' UTR of mRNAs coding for the capsid proteins repressed VP1 and VP2 protein synthesis, (ii) the 3' UTR did not affect nuclear export or mRNA stability, and (iii) mRNAs bearing the 3' UTR of the capsid protein mRNAs did not associate with ribosomes at all. Taken together, these results indicate that in nonpermissive cells, the 3' UTR of the capsid protein mRNAs represses capsid protein synthesis at the translational level by inhibiting ribosome loading.
Pallier
C
C
Unité de Virologie, and CNRS UPR 9051, Hôpital Saint-Louis, Paris, France.
Greco
A
A
Le Junter
J
J
Saib
A
A
Vassias
I
I
Morinet
F
F
D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002213:Capsid / Q000235:genetics*; D036022:Capsid Proteins; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006801:Humans; D016732:Parvovirus B19, Human / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger; D012367:RNA, Viral / Q000235:genetics*; D011817:Rabbits; D014158:Transcription, Genetic
D036022:Capsid Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; C095547:capsid protein VP1, parvovirus B19; C095548:capsid protein VP2, parvovirus B19