Internal polyadenylation of parvoviral precursor mRNA limits progeny virus production

Qinfeng Huang, Xuefeng Deng, Sonja M. Best, Marshall E. Bloom, Yi Li, Jianming Qiu

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Aleutian Mink Disease Virus (AMDV) is the only virus in the genus Amdovirus of family Parvoviridae. In adult mink, AMDV causes a persistent infection associated with severe dysfunction of the immune system. Cleavage of AMDV capsid proteins has been previously shown to play a role in regulating progeny virus production (Fang Cheng et al., J. Virol. 84:2687-2696, 2010). The present study shows that AMDV has evolved a second strategy to limit expression of capsid proteins by preventing processing of the full-length capsid protein-encoding mRNA transcripts. Characterization of the cis-elements of the proximal polyadenylation site [(pA)p] in the infectious clone of AMDV revealed that polyadenylation at the (pA)p site is controlled by an upstream element (USE) of 200 nts in length, the AAUAAA signal, and a downstream element (DSE) of 40 nts. A decrease in polyadenylation at the (pA)p site, either by mutating the AAUAAA signal or the DSE, which does not affect the encoding of amino acids in the infectious clone, increased the expression of capsid protein VP1/VP2 and thereby increased progeny virus production approximately 2-3-fold. This increase was accompanied by enhanced replication of the AMDV genome. Thus, this study reveals correlations among internal polyadenylation, capsid production, viral DNA replication and progeny virus production of AMDV, indicating that internal polyadenylation is a limiting step for parvovirus replication and progeny virus production.

Original languageEnglish (US)
Pages (from-to)167-177
Number of pages11
JournalVirology
Volume426
Issue number2
DOIs
StatePublished - May 10 2012

Bibliographical note

Funding Information:
This work was supported by PHS grant R01 AI070723 and R21 AI085236 , and was supported in part by the Intramural Research Program of the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID). We thank members in the Qiu lab for valuable discussions, and are indebted to Fang Cheng for excellent technical support.

Keywords

  • Parvovirus
  • Polyadenylation
  • Virus production

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