The Small 11 kDa Nonstructural Protein of Human Parvovirus B19 Plays a Key Role in Inducing Apoptosis During B19 Virus Infection of Primary Erythroid Progenitor Cells

Blood. 2010 Feb 4;115(5):1070-80. doi: 10.1182/blood-2009-04-215756. Epub 2009 Oct 27.

Abstract

Human parvovirus B19 (B19V) infection shows a strong erythroid tropism and drastically destroys erythroid progenitor cells, thus leading to most of the disease outcomes associated with B19V infection. In this study, we systematically examined the 3 B19V nonstructural proteins, 7.5 kDa, 11 kDa, and NS1, for their function in inducing apoptosis in transfection of primary ex vivo-expanded erythroid progenitor cells, in comparison with apoptosis induced during B19V infection. Our results show that 11 kDa is a more significant inducer of apoptosis than NS1, whereas 7.5 kDa does not induce apoptosis. Furthermore, we determined that caspase-10, an initiator caspase in death receptor signaling, is the most active caspase in apoptotic erythroid progenitors induced by 11 kDa and NS1 as well as during B19V infection. More importantly, cytoplasm-localized 11 kDa is expressed at least 100 times more than nucleus-localized NS1 at the protein level in primary erythroid progenitor cells infected with B19V; and inhibition of 11 kDa expression using antisense oligos targeting specifically to the 11 kDa-encoding mRNAs reduces apoptosis significantly during B19V infection of erythroid progenitor cells. Taken together, these results demonstrate that the 11 kDa protein contributes to erythroid progenitor cell death during B19V infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis*
  • Caspase 10 / metabolism
  • Caspase Inhibitors
  • Cell Line
  • Cells, Cultured
  • Cysteine Proteinase Inhibitors / pharmacology
  • Erythroid Precursor Cells / cytology
  • Erythroid Precursor Cells / metabolism*
  • Erythroid Precursor Cells / virology
  • Flow Cytometry
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Immunoblotting
  • In Situ Nick-End Labeling
  • K562 Cells
  • Molecular Weight
  • Parvovirus B19, Human / genetics*
  • Parvovirus B19, Human / metabolism
  • Parvovirus B19, Human / physiology
  • Quinolines / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / physiology

Substances

  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Quinolines
  • Viral Nonstructural Proteins
  • quinoline-val-asp(OMe)-CH2-OPH
  • Caspase 10