Inhibition of Host Gene Expression by KSHV: Sabotaging mRNA Stability and Nuclear Export.

Carissa Ikka Pardamean,Ting-Ting Wu

doi:10.3389/fcimb.2021.648055

Carissa Ikka Pardamean, Ting-Ting Wu

Open Access

https://doi.org/10.3389/fcimb.2021.648055

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Abstract

Viruses are known for their ability to alter host gene expression. Kaposi sarcoma-associated herpesvirus has two proteins that obstruct host gene expression. KSHV SOX, encoded by the open reading frame 37 (ORF37), induces a widespread cytoplasmic mRNA degradation and a block on mRNA nuclear export. The other KSHV protein, encoded by the open reading frame 10 (ORF10), was recently identified to inhibit host gene expression through its direct function on the cellular mRNA export pathway. In this review, we summarize the studies on both SOX and ORF10 in efforts to elucidate their mechanisms. We also discuss how the findings based on a closely related rodent virus, murine gammaherpesvirus-68 (MHV-68), complement the KSHV findings to decipher the role of these two proteins in viral pathogenesis.

Highlights

Kaposi sarcoma-associated herpesvirus (KSHV), or the human herpesvirus-8 (HHV-8), belongs to the gamma subfamily of herpesviruses
We have shown that KSHV and murine gammaherpesvirus-68 (MHV-68) open reading frame 10 (ORF10) induce nuclear accumulation of poly(A) RNA, which is abolished by mutations that disrupt ORF10-Rae1 interaction or Rae1 knockdown
While shutoff and exonuclease (SOX) and ORF10 are capable of inhibiting host gene expression, their functions during gammaherpesvirus infection do not overlap

Summary

Introduction

Kaposi sarcoma-associated herpesvirus (KSHV), or the human herpesvirus-8 (HHV-8), belongs to the gamma subfamily of herpesviruses. The best studied KSHV protein to inhibit host gene expression is the shutoff and exonuclease (SOX) protein encoded by KSHV ORF37 (Glaunsinger and Ganem, 2004), which accelerates cytoplasmic mRNA degradation. Frequently employed by RNA viruses, targets mRNA nuclear export to inhibit host gene expression (Yarbrough et al, 2014). We identified KSHV ORF10 as another inhibitor of host gene expression by interacting with a cellular mRNA export factor, Rae1.

Results

Conclusion