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  • Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1.

Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1.

Veterinary microbiology (2020-10-02)
Yanrong Zhou, Zhenzhen Hou, Liurong Fang, Qiyun Ke, Yujian Xiong, Puxian Fang, Shaobo Xiao
ABSTRACT

Like obligate intracellular parasites, viruses co-opt host cell resources to establish productive infections. Polyamines are key aliphatic molecules that perform important roles in cellular growth and proliferation. They are also needed for the successful multiplication of various viruses. Little is known about the effects of polyamines on Arteriviridae infections. Here, porcine reproductive and respiratory syndrome virus (PRRSV), an economically prominent porcine virus, was used to investigate virus-polyamine interactions. We found that PRRSV infection significantly downregulated the levels of cellular polyamines. Using an inhibitor or specific short interfering RNAs (siRNAs) of ornithine decarboxylase 1, a key anabolic enzyme involved in the classical de novo biosynthesis of polyamines, we found that polyamine depletion abrogated PRRSV proliferation, and this effect was recoverable by adding exogenous spermidine and spermine, but not putrescine to the cells, suggesting that the host inhibits polyamine biosynthesis to restrict PRRSV proliferation. Further analysis revealed that the expression level of spermidine-spermine acetyltransferase 1 (SAT1), a catabolic enzyme that reduces spermidine and spermine levels, was upregulated during PRRSV infection, but conversely, SAT1 had an inhibitory effect on PRRSV reproduction. Our data show that polyamines are important molecules during PRRSV-host interactions, and polyamines and their biosynthetic pathways are potential therapeutic targets against PRRSV infection.

MATERIALS
Product Number
Brand
Product Description

Supelco
Putrescine, analytical standard
Sigma-Aldrich
Dansyl chloride, BioReagent, suitable for amino acid labeling, powder and chunks, ≥99% (HPLC)
Sigma-Aldrich
Putrescine dihydrochloride, ≥98% (TLC)
Sigma-Aldrich
DL-α-Difluoromethylornithine hydrochloride hydrate, solid, ≥97% (NMR)
Sigma-Aldrich
Polyamine Supplement (1000×), liquid, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Spermine tetrahydrochloride, powder or crystals
Sigma-Aldrich
Spermidine, BioReagent, for molecular biology, suitable for cell culture, ≥98%
Sigma-Aldrich
Spermidine trihydrochloride, ≥98% (TLC)
Supelco
Spermine, analytical standard