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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

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KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5

R Santarelli1, M Granato1, G Pentassuglia1

  • 1a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.

Autophagy
|October 8, 2016
PubMed

Insights

Kaposi sarcoma-associated herpesvirus (KSHV) hinders dendritic cell (DC) formation by inhibiting autophagy, a key process for immune cell development. This viral strategy reduces calpastatin and ATG5, aiding immune evasion and viral malignancy progression.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Kaposi sarcoma-associated herpesvirus (KSHV) is known to impede monocyte differentiation into dendritic cells (DCs).
  • Autophagy is crucial for the differentiation of monocytes into DCs.

Purpose of the Study:

  • To investigate the mechanism by which KSHV impairs DC formation.
  • To elucidate the role of autophagy inhibition in KSHV-mediated immune evasion.

Main Methods:

  • Utilized THP-1 monocytoid cells and primary human monocytes.
  • Assessed the impact of KSHV infection on autophagy markers, including calpastatin (CAST) and ATG5 expression.

Main Results:

  • KSHV infection inhibits autophagy, leading to impaired dendritic cell differentiation.
  • KSHV reduces calpastatin (CAST) levels, which in turn decreases ATG5 expression.
  • This mechanism was observed in both cell lines and primary monocytes.

Conclusions:

  • KSHV employs autophagy inhibition as a novel strategy to escape immune surveillance.
  • Understanding this viral immune suppressive mechanism is vital for developing new therapies against KSHV-associated malignancies.
Keywords:
ATG5CAPN/calpainCAST/calpastatinKSHVMAPK/JNKSQSTM1/p62THP-1autophagydendritic cellsherpesvirusmonocytes

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