Ectopic expression of murine CD163 enables cell-culture isolation of lactate dehydrogenase-elevating virus 63 years after its discovery

J Virol. 2023 Oct 31;97(10):e0093023. doi: 10.1128/jvi.00930-23. Epub 2023 Oct 4.

Abstract

Mouse models of viral infection play an especially large role in virology. In 1960, a mouse virus, lactate dehydrogenase-elevating virus (LDV), was discovered and found to have the peculiar ability to evade clearance by the immune system, enabling it to persistently infect an individual mouse for its entire lifespan without causing overt disease. However, researchers were unable to grow LDV in culture, ultimately resulting in the demise of this system as a model of failed immunity. We solve this problem by identifying the cell-surface molecule CD163 as the critical missing component in cell-culture systems, enabling the growth of LDV in immortalized cell lines for the first time. This advance creates abundant opportunities for further characterizing LDV in order to study both failed immunity and the family of viruses to which LDV belongs, Arteriviridae (aka, arteriviruses).

Keywords: CD163; PRRSV; SHFV; arterivirus; lactate dehydrogenase-elevating virus; porcine reproductive and respiratory syndrome virus; simian hemorrhagic fever virus.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD* / genetics
  • Antigens, CD* / metabolism
  • Antigens, Differentiation, Myelomonocytic* / genetics
  • Antigens, Differentiation, Myelomonocytic* / metabolism
  • Cell Culture Techniques*
  • Cell Line / virology
  • Ectopic Gene Expression*
  • Lactate dehydrogenase-elevating virus* / genetics
  • Lactate dehydrogenase-elevating virus* / growth & development
  • Lactate dehydrogenase-elevating virus* / immunology
  • Lactate dehydrogenase-elevating virus* / metabolism
  • Mice
  • Receptors, Cell Surface* / genetics
  • Receptors, Cell Surface* / metabolism
  • Time Factors

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Receptors, Cell Surface