J Bacteriol Virol.  2016 Dec;46(4):326-329. 10.4167/jbv.2016.46.4.326.

Functions of Herpesvirus-Encoded Homologs of the Cellular Ribonucleotide Reductase Large Subunit

• Kwon KM
• Ahn JH

• KMID: 2366881
• DOI: http://doi.org/10.4167/jbv.2016.46.4.326

Abstract

Deoxyribonucleotides (dNTPs) are important for the efficient growth of DNA viruses. Therefore, many DNA viruses have strategies for the upregulation of cellular dNTP levels. Both α- and γ-herpesviruses encode functional homologs of cellular dNTP anabolic enzymes, including the class I ribonucleotide reductase (RNR) large (R1) and small (R2) subunits, whereas β-herpesviruses modulate host cells to induce genes that increase dNTP levels. Interestingly, β-herpesviruses still express the nonfunctional RNR R1 subunit. However, it is not clear why β-herpesviruses still carry inactive R1 homologs. Recently, the R1 homologs of herpesviruses have been shown to inhibit innate immune signaling pathways. In particular, both functional and nonfunctional R1 homologs target receptor-interacting protein kinase 1 (RIP1) and inhibit RIP1-mediated signaling pathways to promote viral replication. Here, we summarize recent findings on the activity of herpesviral R1 homologs and discuss their roles in the regulation of innate immune signaling pathways.

Keyword

Herpesvirus; Ribonucleotide reductase large subunit; Immune signaling

MeSH Terms

Deoxyribonucleotides
DNA Viruses
Herpesviridae
Protein Kinases
Ribonucleotide Reductases*
Up-Regulation
Deoxyribonucleotides
Protein Kinases
Ribonucleotide Reductases

Figure

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  Figure 1. Distribution and organization of herpesvirus R1 proteins. (A) Unlike human α- and γ-herpesviruses, human β-herpesviruses lack genes encoding the RNR R2 subunit and thymidine kinase and encode a nonfunctional RNR R1 subunit and dUTPase. (B) The C-terminal region of β-herpesvirus R1 proteins shares homology with other viral counterparts, but lacks most of the residues known to have a direct catalytic role. The proposed nucleotide-binding site (GxGxxG) and the catalytically active sites, i.e., five cysteines and two tyrosines (2), are shown. NF: nonfunctional.

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