Apprehending the NAD⁺-ADPr-Dependent Systems in the Virus World

Lakshminarayan M Iyer¹, A Maxwell Burroughs¹, Vivek Anantharaman¹

¹National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

|September 23, 2022

Summary

This study explores how viruses use NAD+ and ADP-ribose (ADPr) systems during infection. Researchers analyzed 21,191 viral proteomes to identify ADPr-related proteins. They found that these proteins are frequently packaged into virions, especially in phages with contractile tails. The study suggests that ADPr systems help viruses modify host molecules and counter NAD+-derived signals. The findings show that ADPr-related genes are exchanged between viruses and hosts. The authors propose that phage ADPr systems target soluble ADPr derivatives, while eukaryotic viruses prefer macromolecular adducts. The study also predicts host systems that counter viral ADPr modifications.

Area of Science:

Virology
Molecular biology
Host-pathogen interactions

Background:

The role of NAD+ and ADP-ribose (ADPr) in virus-host interactions remains underexplored. Prior research has shown these molecules regulate RNA processing and immune signaling. However, the extent of their involvement in viral strategies is unclear. No prior work had resolved how ADPr systems are distributed across viral lineages. This gap motivated a systematic analysis of viral proteomes. The study aimed to uncover patterns in ADPr utilization across viruses. Existing knowledge lacks clarity on the evolutionary exchange of ADPr-related genes. This paper addresses that uncertainty by analyzing 21,191 viral proteomes.

Purpose Of The Study:

The study aimed to map NAD+-ADPr systems across viral lineages. Researchers focused on identifying key components of these systems. They sought to determine how frequently ADPr-related proteins appear in viral proteomes. The goal was to assess the evolutionary distribution of these systems. The team also aimed to predict host systems that counter viral ADPr modifications. By analyzing 21,191 viral proteomes, they aimed to reveal patterns. The study aimed to clarify how ADPr systems are repurposed by viruses. The purpose was to understand the functional roles of ADPr in viral infection.

Main Methods:

The team used comparative genomics to analyze 21,191 viral proteomes. They identified ADPr-related domains in viral proteins using sequence analysis. The researchers focused on ADP-ribosyltransferases (ARTs) and Nudix hydrolases. They examined the presence of these domains in different viral groups. The study included positive-strand RNA and DNA viruses with large genomes. The team compared viral ADPr systems with host and symbiont sequences. They used contextual analysis to infer functional roles of ADPr domains. The methods included reconstructing evolutionary relationships between viral and host ADPr systems.

Main Results:

ADPr-related domains were frequently found in phages with contractile tails. ARTs, Nudix, and NADAR proteins were commonly packaged into virions. These proteins modify host macromolecules during infection. The study found repeated gene exchange between viruses and hosts. Eukaryotic RNA viruses prefer macromolecular ADPr adducts. Bacteriophages likely target soluble ADPr derivatives. The results show ADPr systems are exploited by viruses with complex life cycles. Comparative genomics predicted host systems that counter viral ADPr modifications.

Conclusions:

The authors propose that ADPr systems are central to virus-host conflicts. They suggest that ADPr-related proteins are deployed during infection to modify host signals. The study indicates these systems are widely exploited by RNA and DNA viruses. The findings show ADPr domains are frequently exchanged between viruses and hosts. The authors propose that phage ADPr systems counter soluble ADPr derivatives. They suggest eukaryotic viruses target macromolecular ADPr adducts. The study concludes that ADPr systems are evolutionarily selected across viral lineages. The results suggest host systems exist to counter viral ADPr modifications.

Keywords:

ADP-ribose ADP-ribosyltransferase NADase RNA polymerase RNA repair anti-phage systems cyclic ADP-ribose nicotinamide adenine dinucleotide nucleotides sirtuin virus evolution virus-host interactions NAD+ADP-ribose comparative genomics

Frequently Asked Questions

According to the authors, ADPr systems are used by viruses to modify host macromolecules and counter NAD+-derived signals during infection.

The study found that phages with contractile tails, specifically Myoviruses, frequently package ADPr-related proteins into virions.

The authors propose that viruses with larger genomes and more complex life strategies exploit ADPr systems to manipulate host processes.

Contextual analysis suggests bacteriophage ADPr domains target soluble derivatives, while eukaryotic RNA viruses prefer macromolecular adducts.

The study found repeated exchange of ADPr-related genes between viruses, hosts, and endo-parasites, suggesting evolutionary selection for these systems.

Comparative genomics predicted host systems involved in countering viral ADP ribosylation of host molecules.