THE 3'-UNTRANSLATED REGION OF THE B19 PARVOVIRUS CAPSID PROTEIN MESSENGER-RNAS INHIBITS ITS OWN MESSENGER-RNA TRANSLATION IN NONPERMISSIVE CELLS

Although parvoviruses are found throughout the animal kingdom, only th e human pathogenic B19 virus has so far been shown to possess a limite d host range, with erythroid progenitor cells as the main target cells supporting B19 propagation. The underlying mechanism of such erythroi d tropism is still unexplained, Synthesis of the NS1 nonstructural pro tein occurs in permissive and nonpermissive cells, such as megakaryocy tes, whereas synthesis of the VP1 and VP2 capsid proteins seems to be restricted to burst-forming units arid CFU of erythroid cells. In nonp ermissive cells, the NS1 protein is overexpressed and the NS1 RNAs are the predominant RNA species, However, the VP1 and VP2 proteins are no t detectable, although the corresponding mRNAs are synthesized, Since all transcripts have part of the 5' untranslated region (5' UTR) in co mmon but distinct 3' UTRs characterizing the nonstructural-and structu ral-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 rep ressed VP1 and VP2 protein synthesis, (ii) the 3' UTR did not affect n uclear expert or mRNA stability, and (iii) mRNAs bearing the 3' UTR of the capsid protein mRNAs did not associate with ribosomes at all, Tak en together, these results indicate that in nonpermissive cells, the 3 ' UTR of the capsid protein mRNAs represses capsid protein synthesis a t the translational level by inhibiting ribosome loading.