Polyamines and Their Role in Virus Infection

Abstract

Polyamines are small, abundant, aliphatic molecules present in all mammalian cells. Within the context of the cell, they play a myriad of roles, from modulating nucleic acid conformation to promoting cellular proliferation and signaling. In addition, polyamines have emerged as important molecules in virus-host interactions. Many viruses have been shown to require polyamines for one or more aspects of their replication cycle, including DNA and RNA polymerization, nucleic acid packaging, and protein synthesis. Understanding the role of polyamines has become easier with the application of small-molecule inhibitors of polyamine synthesis and the use of interferon-induced regulators of polyamines. Here we review the diverse mechanisms in which viruses require polyamines and investigate blocking polyamine synthesis as a potential broad-spectrum antiviral approach.

Keywords: DNA virus; RNA virus; eIF5A; polyamines.

FIG 1

The mammalian biogenic polyamines and metabolic pathways. The polyamines putrescine, spermidine, and spermine (A) are synthesized from the ornithine precursor via a series of enzymatic reactions (B) that elongate the structure of the polyamine and add amino groups. Amino groups are protonated at physiological pH and comprise the aliphatic properties of the polyamines. The biogenic polyamines are highlighted in purple. Anabolic enzymes that promote the synthesis of polyamines are displayed in green, while catabolic enzymes are displayed in orange. Pharmaceuticals targeting the polyamine pathway are highlighted in red. AZIN1, antizyme inhibitor; MTA, 5'-methylthioadenosine; DHPS, deoxyhypusine synthase; SMO, spermine oxidase.

FIG 2

Polyamines in the context of the cell. Polyamines play diverse roles within the cell and alter many of the cellular processes that viruses rely on for their replication, including RNA and DNA structure, protein synthesis and hypusination, membrane interactions, and protein-RNA interactions, as highlighted. AUF1, heteronuclear RNA binding protein D; UTR, untranslated region; HuR, embryonic lethal abnormal vision system human homologue 1.