White Spot Syndrome Virus Protein Kinase 1 Defeats the Host Cell's Iron-Withholding Defense Mechanism by Interacting with Host Ferritin

Lin, Shin-Jen; Lee, Der-Yen; Wang, Hao Ching; Kang, Shih-Ting; Hwang, Pung‐Pung; Kou, Guang Hsiung; Huang, Ming-Fen; Chang, Geen-Dong; Lo, Chu Fang

doi:10.1128/jvi.02318-14

Cited by 23 publications

(15 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, Nipah virus matrix protein inhibits the host IB kinase epsilon (IKK) kinase-mediated IFN type I antiviral response by targeting the host E3-ubiquitin ligase TRIM6 (45). A recent study revealed that the WSSV genome can encode protein kinase 1 to defeat the host cell's iron-withholding defense mechanism by interacting with host ferritin (46). In this context, viruses possess complicated mechanisms to escape the host immunity.…”

Section: Discussionmentioning

confidence: 99%

Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp

Ren

Huang

Cui

et al. 2017

J Virol

View full text Add to dashboard Cite

In eukaryotes, microRNAs (miRNAs) serve as regulators of many biological processes, including virus infection. An miRNA can generally target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs has not yet been extensively explored during virus infection. This study found that the Spaztle (Spz)-Toll-Dorsal-antilipopolysaccharide factor (ALF) signaling pathway plays a very important role in antiviral immunity against invasion of white spot syndrome virus (WSSV) in shrimp (Marsupenaeus japonicus). Dorsal, the central gene in the Toll pathway, was targeted by two viral miRNAs (WSSV-miR-N13 and WSSV-miR-N23) during WSSV infection. The regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo, leading to virus infection. Our study contributes novel insights into the viral miRNAmediated Toll signaling pathway during the virus-host interaction.IMPORTANCE An miRNA can target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs during virus infection has not yet been extensively explored. The results of this study indicated that the shrimp Dorsal gene, the central gene in the Toll pathway, was targeted by two viral miRNAs during infection with white spot syndrome virus. Regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo, leading to virus infection. Our study provides new insight into the viral miRNA-mediated Toll signaling pathway in virus-host interactions.

show abstract

Section: Discussionmentioning

confidence: 99%

Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp

Ren

Huang

Cui

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…In response to this, hosts have evolved mechanisms through which they can withhold iron from pathogens, thereby inhibiting their proliferation. The protein responsible for this mechanism is ferritin [ 105 ]. The ferritin defense mechanism has been demonstrated in L. vannamei , where its injection reduced susceptibility to WSSV infection.…”

Section: Wssv Infectionmentioning

confidence: 99%

“…Conversely, dsRNA-mediated knockdown of ferritin resulted in a three-fold increase in viral copy number [ 165 ]. Through the use of a yeast two-hybrid experiment, it has been shown that WSSV protein kinase 1 (WSSV PK1) can interact with host ferritin and influence the availability of iron [ 105 ]. Binding of WSSV PK1 does not release iron from ferritin but rather prevents iron from binding to apoferritin (ferritin without bound iron).…”

Section: Wssv Infectionmentioning

confidence: 99%

Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

Verbruggen

Bickley

Aerle

et al. 2016

Viruses

184

View full text Add to dashboard Cite

Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.

show abstract

“…Protein kinase 1 of WSSV interacts with shrimp ferritin and prevents it from iron loading, and thus stabilizes the cellular labile iron pool. This may be an assault mechanism of WSSV to counteract the host cell's iron-withholding defense mechanism [50]. Ferritin synthesis has been reported to be increased in mengovirusinfected cells to combat with the increased levels of free iron after virus infection [51].…”

Section: Discussionmentioning

confidence: 99%

Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion

Ojha

Lole

2016

Mol Cell Biochem

View full text Add to dashboard Cite

Hepatitis E Virus (HEV) is the major causative agent of acute hepatitis in developing countries. Its genome has three open reading frames (ORFs)-called as ORF1, ORF2, and ORF3. ORF1 encodes nonstructural polyprotein having multiple domains, namely: Methyltransferase, Y domain, Protease, Macro domain, Helicase, and RNA-dependent RNA polymerase. In the present study, we show that HEV-macro domain specifically interacts with light chain subunit of human ferritin (FTL). In cultured hepatoma cells, HEV-macro domain reduces secretion of ferritin without causing any change in the expression levels of FTL. This inhibitory effect was further enhanced upon Brefeldin-A treatment. The levels of transferrin Receptor 1 or ferroportin, two important proteins in iron metabolism, remained unchanged in HEV-macro domain expressing cells. Similarly, there were no alterations in the levels of cellular labile iron pool and reactive oxygen species, indicating that HEV-macro domain does not influence cellular iron homeostasis/metabolism. As ferritin is an acute-phase protein, secreted in higher level in infected persons and HEV-macro domain has the property of reducing synthesis of inflammatory cytokines, we propose that by directly binding to FTL, macro domain prevents ferritin from entering into circulation and helps in further attenuation of the host immune response.

show abstract

White Spot Syndrome Virus Protein Kinase 1 Defeats the Host Cell's Iron-Withholding Defense Mechanism by Interacting with Host Ferritin

Cited by 23 publications

References 48 publications

Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp

Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp

Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion

Contact Info

Product

Resources

About