Distinct MCM10 Proteasomal Degradation Profiles by Primate Lentiviruses Vpr Proteins.

Hao Chang,Chieh-Wen Lo,Hiroyuki Otsuki,Lowela Siarot,Hirotaka Sato,Ryosuke Matsuura,Yoko Aida

doi:10.3390/v12010098

Hao Chang, Chieh-Wen Lo + Show 5 more

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https://doi.org/10.3390/v12010098

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Abstract

Viral protein R (Vpr) is an accessory protein found in various primate lentiviruses, including human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) as well as simian immunodeficiency viruses (SIVs). Vpr modulates many processes during viral lifecycle via interaction with several of cellular targets. Previous studies showed that HIV-1 Vpr strengthened degradation of Mini-chromosome Maintenance Protein10 (MCM10) by manipulating DCAF1-Cul4-E3 ligase in proteasome-dependent pathway. However, whether Vpr from other primate lentiviruses are also associated with MCM10 degradation and the ensuing impact remain unknown. Based on phylogenetic analyses, a panel of primate lentiviruses Vpr/x covering main virus lineages was prepared. Distinct MCM10 degradation profiles were mapped and HIV-1, SIVmus and SIVrcm Vprs induced MCM10 degradation in proteasome-dependent pathway. Colocalization and interaction between MCM10 with these Vprs were also observed. Moreover, MCM10 2-7 interaction region was identified as a determinant region susceptible to degradation. However, MCM10 degradation did not alleviate DNA damage response induced by these Vpr proteins. MCM10 degradation by HIV-1 Vpr proteins was correlated with G2/M arrest, while induction of apoptosis and oligomerization formation of Vpr failed to alter MCM10 proteolysis. The current study demonstrated a distinct interplay pattern between primate lentiviruses Vpr proteins and MCM10.

Highlights

During long co-evolutionary history, viral pathogens keep developing increasingly novel weapons which against hosts to facilitate viral survival and pathogenesis, via encoding structural and enzymatic proteins and various accessory proteins where required
The current study firstly investigated whether Mini-chromosome Maintenance Protein10 (MCM10) degradation by primate lentiviruses Viral protein R (Vpr) occurs and whether it was correlated with viral lineages
We investigated whether endogenous MCM10 protein expression levels were susceptible to HIV-1, SIVmus, and SIVrcm Vpr proteins

Summary

Introduction

During long co-evolutionary history, viral pathogens keep developing increasingly novel weapons which against hosts to facilitate viral survival and pathogenesis, via encoding structural and enzymatic proteins and various accessory proteins where required. Human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) and other primate lentiviruses encode accessory proteins that enhance viral infectivity [1]. These include Viral protein R (Vpr), Viral infectivity factor (Vif), Viral protein U (Vpu), and negative regulation factor (Nef). Viruses 2020, 12, 98 lentiviruses, including HIV-2 and simian immunodeficiency virus (SIV), encode a paralog of Vpr termed Viral protein X (Vpx). Viral protein Rs (Vprs) are multifunctional accessory proteins, found among all primate lentiviruses, including HIV-1 and HIV-2 and various SIVs. A striking feature of Vpr is its unique potential to promote viral productivity in monocytes/macrophages and in a small population of CD4+ T cells [2]

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