N-myc downstream-regulated gene 1 facilitates influenza A virus replication by suppressing canonical NF-κB signaling

Chen, Lin; Xing, Chao; Ma, Guoyao; Luo, Jing; Su, Wen; Li, Meng; Shi, Qiumei; He, Hongxuan

doi:10.1016/j.virusres.2018.05.001

Cited by 12 publications

(13 citation statements)

References 28 publications

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“…NDRG1 has been implicated in many cellular functions, including stress responses (17), cell growth (19), cell differentiation (18), vesicular trafficking (21), apoptosis (22), and autophagy (28). It is also reported to restrict HCV propagation (29) but to facilitate IAV replication (30). Therefore, the molecular mechanisms underlying the involvement of NDRG1 in viral replication vary markedly.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, NDRG1 has been shown to restrict the propagation of hepatitis C virus (HCV) by inhibiting viral assembly (29). On the contrary, Chen et al found that NDRG1 facilitates influenza A virus (IAV) replication by suppressing canonical NF-κB signaling (30). However, the role of NDRG1 in the PRRSV life cycle requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

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Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To Facilitate Viral Replication through Downregulation of NDRG1 Expression

Wang

Liu

KeYu

et al. 2019

J Virol

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Autophagy maintains cellular homeostasis by degrading organelles, proteins, and lipids in lysosomes. Autophagy is involved in the innate and adaptive immune responses to a variety of pathogens. Some viruses can hijack host autophagy to enhance their replication. However, the role of autophagy in porcine reproductive and respiratory syndrome virus (PRRSV) infection is unclear. Here, we show that N-Myc downstream-regulated gene 1 (NDRG1) deficiency induced autophagy, which facilitated PRRSV replication by regulating lipid metabolism. NDRG1 mRNA is expressed ubiquitously in most porcine tissues and most strongly in white adipose tissue. PRRSV infection downregulated the expression of NDRG1 mRNA and protein, while NDRG1 deficiency contributed to PRRSV RNA replication and progeny virus assembly. NDRG1 deficiency reduced the number of intracellular lipid droplets (LDs), but the expression levels of key genes in lipogenesis and lipolysis were not altered. Our results also show that NDRG1 deficiency promoted autophagy and increased the subsequent yields of hydrolyzed free fatty acids (FFAs). The reduced LD numbers, increased FFA levels, and enhanced PRRSV replication were abrogated in the presence of an autophagy inhibitor. Overall, our findings suggest that NDRG1 plays a negative role in PRRSV replication by suppressing autophagy and LD degradation. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped single-positive-stranded RNA virus, causes acute respiratory distress in piglets and reproductive failure in sows. It has led to tremendous economic losses in the swine industry worldwide since it was first documented in the late 1980s. Vaccination is currently the major strategy used to control the disease. However, conventional vaccines and other strategies do not provide satisfactory or sustainable prevention. Therefore, safe and effective strategies to control PRRSV are urgently required. The significance of our research is that we demonstrate a previously unreported relationship between PRRSV, NDRG1, and lipophagy in the context of viral infection. Furthermore, our data point to a new role for NDRG1 in autophagy and lipid metabolism. Thus, NDRG1 and lipophagy will have significant implications for understanding PRRSV pathogenesis for developing new therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To Facilitate Viral Replication through Downregulation of NDRG1 Expression

Wang

Liu

KeYu

et al. 2019

J Virol

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“…Another study also showed that NDRG1 restricts hepatitis C virus propagation by regulating lipid droplet formation and viral assembly [53]. On the other hand, a study published this year reported that NDRG1 facilitates influenza A virus replication by suppressing canonical NF-kappa B signaling [54]. All of these studies suggest that NDRG1 may participate in the viral life cycle, but the functions of this protein appear to be diverse.…”

Section: Discussionmentioning

confidence: 99%

NDRG1 facilitates the replication and persistence of Kaposi’s sarcoma-associated herpesvirus by interacting with the DNA polymerase clamp PCNA

et al. 2019

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Kaposi’s sarcoma-associated herpesvirus (KSHV) latently infects host cells and establishes lifelong persistence as an extra-chromosomal episome in the nucleus. To persist in proliferating cells, the viral genome typically replicates once per cell cycle and is distributed into daughter cells. This process involves host machinery utilized by KSHV, however the underlying mechanisms are not fully elucidated. In present study, we found that N-Myc downstream regulated gene 1 (NDRG1), a cellular gene known to be non-detectable in primary B cells and endothelial cells which are the major cell types for KSHV infection in vivo, was highly upregulated by KSHV in these cells. We further demonstrated that the high expression of NDRG1 was regulated by latency-associated nuclear antigen (LANA), the major viral latent protein which tethers the viral genome to host chromosome and plays an essential role in viral genome maintenance. Surprisingly, knockdown of NDRG1 in KSHV latently infected cells resulted in a significant decrease of viral genome copy number in these cells. Interestingly, NDRG1 can directly interact with proliferating cell nuclear antigen (PCNA), a cellular protein which functions as a DNA polymerase clamp during DNA replication. Intriguingly, we found that NDRG1 forms a complex with LANA and PCNA and serves as a scaffold protein bridging these two proteins. We further demonstrated that NDRG1 is critical for mediating LANA to recruit PCNA onto terminal repeat (TR) of KSHV genome, and facilitates viral DNA replication and episome persistence. Taken together, our findings suggest that NDRG1 plays an important role in KSHV viral genome replication, and provide new clues for understanding of KSHV persistence.

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“…However, the role of ndrG1 in viral infection is ambiguous. ndrG1 limits the life cycle of hepatitis c virus (25) but promotes the replication of influenza A virus (23). The present study identified that the infection of a549 cells with A. fumigatus significantly increased the protein expression of ndrG1, which serves an important role in maintaining the integrity of the lung epithelial cell barrier (26).…”

Section: Discussionmentioning

confidence: 53%

“…ndrG1, a member of the ndrG family (ndrG 1-4), is expressed in epithelial cells (23). ndrG1 is involved in multiple cell biological processes, such as cell proliferation, differentiation and development (24).…”

Section: Discussionmentioning

confidence: 99%

iTRAQ‑based proteomic analysis of the interaction of A549 human lung epithelial cells with Aspergillus fumigatus conidia

Zhang

Gao

et al. 2020

Mol Med Rep

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Severe invasive aspergillosis infection occurs when human immune function is impaired. The interaction between Aspergillus fumigatus (A. fumigatus) conidia and type ii lung epithelial cells serves an important role in disease progression. The present study compared the proteomes of a549 human lung epithelial cells with and without A. fumigatus infection. Gene ontology (Go), Kyoto encyclopedia of Genes and Genomes (KeGG) and protein interaction analyses were performed, and differential protein expression was verified by western blotting and reverse transcription-quantitative Pcr (rT-qPcr). in addition, the rna interference method, an internalization assay and eliSa were performed. isobaric tags for relative and absolute quantification analysis detected a total of 1,582 proteins, from which 111 proteins with differential expression were obtained (fold change >1.5 or <0.75). among them, 18 proteins were upregulated and 93 proteins were downregulated in a549 cells challenged with A. fumigatus. Go and KeGG analyses revealed that the altered proteins were mainly involved in biological functions, such as cell metabolism, synthesis, the cellular stress response, metabolic pathways and pyruvate metabolism. n-myc downstream-regulated gene 1 (ndrG1) expression was upregulated 1.88-fold, while cd44 expression was downregulated 0.47-fold following A. fumigatus infection. The expression levels of specific proteins were verified by western blotting and rT-qPcr. The internalization efficiency was affected by NDRG1 gene silencing. The secretion of il-6 and il-8 was affected when cd44 was inhibited. These results indicated that A. fumigatus affects lung epithelial cell metabolism and biological synthetic functions. a number of novel molecules, including ndrG1 and cd44, were found to be related to A. fumigatus infection.

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N-myc downstream-regulated gene 1 facilitates influenza A virus replication by suppressing canonical NF-κB signaling

Cited by 12 publications

References 28 publications

Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To Facilitate Viral Replication through Downregulation of NDRG1 Expression

Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To Facilitate Viral Replication through Downregulation of NDRG1 Expression

NDRG1 facilitates the replication and persistence of Kaposi’s sarcoma-associated herpesvirus by interacting with the DNA polymerase clamp PCNA

iTRAQ‑based proteomic analysis of the interaction of A549 human lung epithelial cells with Aspergillus fumigatus conidia

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