VP1u phospholipase activity is critical for infectivity of full-length parvovirus B19 genomic clones

Claudia Filippone, Ning Zhi, Susan Wong, Jun Lu, Sachiko Kajigaya, Giorgio Gallinella, Laura Kakkola, Maria Söderlund-Venermo, Neal S Young, Kevin E Brown

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Three full-length genomic clones (pB19-M20, pB19-FL and pB19-HG1) of parvovirus B 19 were produced in different laboratories. pB19-M20 was shown to produce infectious virus. To determine the differences in infectivity, all three plasmids were tested by transfection and infection assays. All three clones were similar in viral DNA replication, RNA transcription, and viral capsid protein production. However, only pB19-M20 and pB19-HG1 produced infectious virus. Comparison of viral sequences showed no significant differences in ITR or NS regions. In the capsid region, there was a nucleotide sequence difference conferring an amino acid substitution (E176K) in the phospholipase A(2)-like motif of the VP1-unique (VP1u) region. The recombinant VP1u with the E176K mutation bad no catalytic activity as compared with the wild-type. When this mutation was introduced into pB19-M20, infectivity was significantly attenuated, confirming the critical role of this motif Investigation of the original serum from which pB19-FL was cloned confirmed that the phospholipase mutation was present in the native B19 virus. (c) 2008 Elsevier Inc. All rights reserved.
Original languageEnglish
JournalVirology
Volume374
Issue number2
Pages (from-to)444-452
Number of pages9
ISSN0042-6822
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Cite this

Filippone, C., Zhi, N., Wong, S., Lu, J., Kajigaya, S., Gallinella, G., ... Brown, K. E. (2008). VP1u phospholipase activity is critical for infectivity of full-length parvovirus B19 genomic clones. Virology, 374(2), 444-452. https://doi.org/10.1016/j.virol.2008.01.002