The non-classical major histocompatibility complex II protein SLA-DM is crucial for African swine fever virus replication

Katrin Pannhorst, Jolene Carlson, Julia E Hölper, Finn Grey, Kenny Baillie, Dirk Höper, Elisabeth Wöhnke, Kati Franzke, Axel Karger, Walter Fuchs, Thomas C Mettenleiter

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

African swine fever virus (ASFV) is a lethal animal pathogen that enters its host cells through endocytosis. So far, host factors specifically required for ASFV replication have been barely identified. In this study a genome-wide CRISPR/Cas9 knockout screen in porcine cells indicated that the genes RFXANK, RFXAP, SLA-DMA, SLA-DMB, and CIITA are important for productive ASFV infection. The proteins encoded by these genes belong to the major histocompatibility complex II (MHC II), or swine leucocyte antigen complex II (SLA II). RFXAP and CIITA are MHC II-specific transcription factors, whereas SLA-DMA/B are subunits of the non-classical MHC II molecule SLA-DM. Targeted knockout of either of these genes led to severe replication defects of different ASFV isolates, reflected by substantially reduced plating efficiency, cell-to-cell spread, progeny virus titers and viral DNA replication. Transgene-based reconstitution of SLA-DMA/B fully restored the replication capacity demonstrating that SLA-DM, which resides in late endosomes, plays a crucial role during early steps of ASFV infection.

Original languageEnglish
Article number10342
Pages (from-to)1-18
Number of pages18
JournalScientific Reports
Volume13
Issue number1
Early online date21 Aug 2023
DOIs
Publication statusPublished - Dec 2023

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Swine
  • African Swine Fever Virus/genetics
  • DNA Replication
  • DNA, Viral
  • Virus Replication/genetics
  • Histocompatibility Antigens Class II/genetics
  • Membrane Proteins
  • Major Histocompatibility Complex
  • African Swine Fever/genetics
  • Craniocerebral Trauma

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