Functional polyamine metabolic enzymes and pathways encoded by the virosphere.

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Viruses hijack host cell metabolism and replication systems to produce progeny.
• Viral genomes often encode metabolic enzymes, acquired from hosts, to manipulate cellular processes.
• The polyamine spermidine is essential for the replication of both bacteriophages and eukaryotic viruses.

Purpose of the Study:

• To identify and functionally characterize viral-encoded polyamine metabolic enzymes and pathways.
• To investigate the role of these viral enzymes in subverting host metabolism for viral replication.
• To consolidate and expand evidence for the global importance of spermidine in virus biology.

Main Methods:

• Bioinformatic analysis to identify viral-encoded polyamine metabolic enzymes and pathways.
• Functional characterization of identified enzymes, including ornithine decarboxylase (ODC), arginine decarboxylase (ADC), arginase, S-adenosylmethionine decarboxylase (AdoMetDC/speD), spermidine synthase, homospermidine synthase, spermidine N-acetyltransferase, and N-acetylspermidine amidohydrolase.
• Identification of homologs of the spermidine-modified translation factor eIF5a in giant viruses.

Main Results:

• Diverse viral enzymes and pathways for spermidine and homospermidine metabolism were identified, including pyridoxal 5'-phosphate (PLP)-dependent ODC, pyruvoyl-dependent ODC and ADC, arginase, AdoMetDC/speD, spermidine synthase, homospermidine synthase, spermidine N-acetyltransferase, and N-acetylspermidine amidohydrolase.
• Some marine phages have evolved AdoMetDC/speD homologs into pyruvoyl-dependent ADC or ODC, and pelagiphages infecting Candidatus Pelagibacter ubique encode both PLP- and pyruvoyl-dependent ADCs.
• Giant viruses encode complete or partial spermidine/homospermidine biosynthetic pathways, and some can release spermidine or sequester it into an inactive N-acetyl form.

Conclusions:

• Viral-encoded enzymes and pathways for spermidine and homospermidine metabolism are widespread and diverse.
• These viral systems play a significant role in manipulating polyamine levels for viral replication.
• The findings underscore a crucial and global role of spermidine in the biology of various viruses.