Diverse Functions of Polyamines in Virus Infection

Firpo, Mason R; Mounce, Bryan C.

doi:10.3390/biom10040628

Cited by 57 publications

(62 citation statements)

References 83 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Polyamines show significant promise as an antiviral target, and this and several other studies show the importance of polyamines in viral infections [7,8]. Repurposing drugs is an efficient way to accelerate antiviral development, as drugs with extensive characterization are better understood in terms of their pharmacokinetics and toxicity profile.…”

Section: Discussionmentioning

confidence: 96%

Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro

Hulsebosch

Mounce

2021

Viruses

Self Cite

View full text Add to dashboard Cite

Enteroviruses, including Coxsackievirus B3 (CVB3), are pervasive pathogens that cause significant disease, including cardiomyopathies. Unfortunately, no treatments or vaccines are available for infected individuals. We identified the host polyamine pathway as a potential drug target, as inhibiting polyamine biosynthesis significantly reduces enterovirus replication in vitro and in vivo. Here, we show that CVB3 is sensitive to polyamine depletion through the polyamine analog diethylnorspermidine (DENSpm), which enhances polyamine catabolism through induction of polyamine acetylation. We demonstrate that CVB3 acquires resistance to DENSpm via mutation of the 2A protease, which enhances proteolytic activity in the presence of DENSpm. Resistance to DENSpm occurred via mutation of a non-catalytic site mutation and results in decreased fitness. These data demonstrate that potential for targeting polyamine catabolism as an antiviral target as well as highlight a potential mechanism of resistance.

show abstract

Section: Discussionmentioning

confidence: 96%

Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro

Hulsebosch

Mounce

2021

Viruses

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several diamine acetyltransferases (SSATs) involved in polyamine catabolic processes were positively modulated in infected P-oysters sampled at 12 hpi. Viruses utilize polyamines for their transcription and translation ( 93 – 95 ). Therefore, by controlling polyamine levels in cells, diamine acetyltransferases act as viral restriction factors that limit virus proliferation ( 94 , 95 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative Proteomics of Ostreid Herpesvirus 1 and Pacific Oyster Interactions With Two Families Exhibiting Contrasted Susceptibility to Viral Infection

Leprêtre

Faury²,

Segarra

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Massive mortality outbreaks affecting Pacific oysters (Crassostrea gigas) spat/juveniles are often associated with the detection of a herpesvirus called ostreid herpesvirus type 1 (OsHV-1). In this work, experimental infection trials of C. gigas spat with OsHV-1 were conducted using two contrasted Pacific oyster families for their susceptibility to viral infection. Live oysters were sampled at 12, 26, and 144 h post infection (hpi) to analyze host-pathogen interactions using comparative proteomics. Shotgun proteomics allowed the detection of seven viral proteins in infected oysters, some of them with potential immunomodulatoy functions. Viral proteins were mainly detected in susceptible oysters sampled at 26 hpi, which correlates with the mortality and viral load observed in this oyster family. Concerning the Pacific oyster proteome, more than 3,000 proteins were identified and contrasted proteomic responses were observed between infected A- and P-oysters, sampled at different post-injection times. Gene ontology (GO) and KEGG pathway enrichment analysis performed on significantly modulated proteins uncover the main immune processes (such as RNA interference, interferon-like pathway, antioxidant defense) which contribute to the defense and resistance of Pacific oysters to viral infection. In the more susceptible Pacific oysters, results suggest that OsHV-1 manipulate the molecular machinery of host immune response, in particular the autophagy system. This immunomodulation may lead to weakening and consecutively triggering death of Pacific oysters. The identification of several highly modulated and defense-related Pacific oyster proteins from the most resistant oysters supports the crucial role played by the innate immune system against OsHV-1 and the viral infection. Our results confirm the implication of proteins involved in an interferon-like pathway for efficient antiviral defenses and suggest that proteins involved in RNA interference process prevent viral replication in C. gigas. Overall, this study shows the interest of multi-omic approaches applied on groups of animals with differing sensitivities and provides novel insight into the interaction between Pacific oyster and OsHV-1 with key proteins involved in viral infection resistance.

show abstract

“…Studies show that MERS-CoV is dependent on polyamines for replication (Mounce et al, 2017). Polyamines are known to control Myc expression, and Myc, in turn, controls the transcription of genes ODC1, SRM and SMS involved in polyamine synthesis (positive feedback loop) (Firpo and Mounce, 2020) (Figure 4). Therefore, the depletion of polyamines can be a strategy to reduce viral infection.…”

Section: Polyamine Metabolismmentioning

confidence: 99%

Host metabolic reprogramming in response to SARS-Cov-2 infection

Moolamalla

Chauhan

Vinod

2020

Preprint

View full text Add to dashboard Cite

Understanding the pathogenesis of SARS-CoV-2 is important for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. How SARS-CoV-2 influences the host metabolism is still unclear. In this study, we analyzed transcriptomic data obtained from different human respiratory cell lines and patient samples (Swab, PBMC, lung biopsy, BALF) to understand the metabolic alterations in response to SARS-CoV-2 infection. For this purpose, the expression pattern of metabolic genes in the human genome-scale metabolic network model Recon3D was explored. We identified metabolic genes and pathways and reporter metabolites under each SARS-CoV-2-infected condition and compared them to identify common and unique changes in the metabolism. Our analysis revealed host-dependent dysregulation of glycolysis, mitochondrial metabolism, amino acid metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. We observed different metabolic changes that are pro- and antiviral in nature. We generated hypotheses on how antiviral metabolism can be targeted/enhanced for reducing viral titers. These warrant further exploration with more samples and in vitro studies to test predictions.

show abstract

Diverse Functions of Polyamines in Virus Infection

Cited by 57 publications

References 83 publications

Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro

Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro

Comparative Proteomics of Ostreid Herpesvirus 1 and Pacific Oyster Interactions With Two Families Exhibiting Contrasted Susceptibility to Viral Infection

Host metabolic reprogramming in response to SARS-Cov-2 infection

Contact Info

Product

Resources

About