The formation and modification of chromatin-like structure of human parvovirus B19 regulate viral genome replication and RNA processing

Virus Res. 2017 Mar 15:232:134-138. doi: 10.1016/j.virusres.2017.03.001. Epub 2017 Mar 2.

Abstract

B19 virus (B19V) is a single stranded virus in the genus of Erythroparvovirus in the family of Parvoviridae. One of the limiting steps of B19V infection is the replication of viral genome which affected the alternative processing of its RNA. Minute virus of mice (MVM) and adeno-associated virus (AAV) has been reported to form chromatin-like structure within hours after infection of cells. However, the role of chromatin-like structure is unclear. In the present study, we found that B19V formed chromatin-like structure after 12h when B19V infectious clone was co-transfected with pHelper plasmid to HEK293T cells. Interestingly, the inhibitor of DNA methyl-transferase (5-Aza-2'-deoxycytidine, DAC) inhibited not only the formation of chromatin-like structure, but also the replication of the viral genomic DNA. More importantly, the splicing of the second intron at splice acceptor sites (A2-1, and A2-2) were reduced and polyadenylation at (pA)p increased when transfected HEK293T cells were treated with DAC. Our results showed that the formation and modification of chromatin-like structure are a new layer to regulate B19V gene expression and RNA processing.

Keywords: B19V; Chromatin-like structure; DAC; RNA splicing; Replication.

MeSH terms

  • Antiviral Agents / pharmacology
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Chromatin / drug effects
  • Chromatin / metabolism*
  • Chromatin / ultrastructure
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • Decitabine
  • Genome, Viral*
  • HEK293 Cells
  • Host-Pathogen Interactions*
  • Humans
  • Parvovirus B19, Human / drug effects
  • Parvovirus B19, Human / genetics*
  • Parvovirus B19, Human / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • RNA Splicing / drug effects
  • RNA, Viral / antagonists & inhibitors
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Chromatin
  • RNA, Viral
  • Viral Proteins
  • Decitabine
  • DNA (Cytosine-5-)-Methyltransferases
  • Azacitidine