The Nucleolar Protein LYAR Facilitates Ribonucleoprotein Assembly of Influenza A Virus

Yang, Cha; Liu, Xiaokun; Gao, Qingxia; Cheng, Tailang; Xiao, Rong; Fan, Ming; Zhang, Shishuo; Jin, Meilin; Chen, Huanchun; Ma, Wenjun; Zhou, Hongbo

doi:10.1128/jvi.01042-18

Cited by 22 publications

(23 citation statements)

References 76 publications

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“…LYAR was shown to be involved in the replication of multiple viruses, including IAV, VSV, and JEV in our previous study (20). Considering that all these viruses are regulated by IFN-I, LYAR might regulate their replication by modulating IFN-I signal pathways.…”

Section: Ifn-␤ Increases the Expression Of Lyar During Virus Infectionmentioning

confidence: 84%

“…Herein, we characterize LYAR as an IFN-␤-inducible gene, which is proposed to have the below double effect on IAV replication. LYAR expression is induced by virus-activated IFN-␤, which is in turn hijacked by influenza A viral RNP to facilitate viral RNA synthesis (20). Simultaneously, LYAR targets IRF3 to suppress the host innate immune responses, providing a favorable environment for virus replication.…”

Section: Discussionmentioning

confidence: 99%

“…All the cell lines listed above were purchased from ATCC (American Type Culture Collection, Manassas, VA, USA). LYAR-KO A549 cells and HEK293T cells were generated as we described previously (20). Sendai virus (Sev) was amplified using 10-day-old embryonic chicken eggs.…”

Section: Methodsmentioning

confidence: 99%

“…LYAR, the cell growth-regulating nucleolar protein, which contains two C2HC-type zinc finger motifs and three nuclear localization signal sequences (NLSs) (19), has been identified as an influenza A viral RNP (vRNP)-interacting partner and facilitated virus replication by stimulating vRNP assembly in our previous study (20). In addition, knocking down LYAR can significantly inhibit not only influenza A virus (IAV) but also vesicular stomatitis virus (VSV) and Japanese encephalitis virus (JEV) replication, indicating that LYAR is involved in the regulation of multiple virus replication events and may utilize a common method in these events.…”

Section: Abstract Innate Immune Responses Ifn-␤ Lyar Irf3mentioning

confidence: 99%

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LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3

Yang

Liu

Cheng

et al. 2019

J Virol

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The innate immune response is vital for host defense and must be tightly controlled, but the mechanisms responsible for its negative regulation are not fully understood. The cell growth-regulating nucleolar protein LYAR was found to promote replication of multiple viruses in our previous study. Here, we report that LYAR acts as a negative regulator of innate immune responses. We found that LYAR expression is induced by beta interferon (IFN-β) during virus infection. Further studies showed that LYAR interacts with phosphorylated IFN regulatory factor 3 (IRF3) to impede the DNA binding capacity of IRF3, thereby suppressing the transcription of IFN-β and downstream IFN-stimulated genes (ISGs). In addition, LYAR inhibits nuclear factor-κB (NF-κB)-mediated expression of proinflammatory cytokines. In summary, our study reveals the mechanism of LYAR in modulating IFN-β-mediated innate immune responses by targeting phosphorylated IRF3, which not only helps us to better understand the mechanisms of LYAR-regulated virus replication but also uncovers a novel role of LYAR in host innate immunity. IMPORTANCE Type I interferon (IFN-I) plays a critical role in the antiviral innate immune responses that protect the host against virus infection. The negative regulators of IFN-I are important not only for fine-tuning the antiviral responses to pathogens but also for preventing excessive inflammation. Identification of negative regulators and study of their modulation in innate immune responses will lead to new strategies for the control of both viral and inflammatory diseases. Here, we report for the first time that the cell growth-regulating nucleolar protein LYAR behaves as a repressor of host innate immune responses. We demonstrate that LYAR negatively regulates IFN-β-mediated immune responses by inhibiting the DNA binding ability of IFN regulatory factor 3 (IRF3). Our study reveals a common mechanism of LYAR in promoting different virus replication events and improves our knowledge of host negative regulation of innate immune responses.

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Section: Ifn-␤ Increases the Expression Of Lyar During Virus Infectionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Abstract Innate Immune Responses Ifn-␤ Lyar Irf3mentioning

confidence: 99%

See 2 more Smart Citations

LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3

Yang

Liu

Cheng

et al. 2019

J Virol

Self Cite

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show abstract

“…The structure, functions, and modulation of the IAV RNA polymerase complex were further discussed by Te Velthuis and Fordor [27]. However, the mechanism of vRNP assembly remains largely unknown and several host proteins were reported to be involved during IAV infection [28][29][30]. Recently, eleuthe roside B 1 was demonstrated to be able to inhibit the vRNP in vitro [31].…”

Section: Iav Viral Proteinsmentioning

confidence: 99%

Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection

Zhang

Cao

2020

Viruses

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Influenza A viruses (IAVs) are highly contagious pathogens infecting human and numerous animals. The viruses cause millions of infection cases and thousands of deaths every year, thus making IAVs a continual threat to global health. Upon IAV infection, host innate immune system is triggered and activated to restrict virus replication and clear pathogens. Subsequently, host adaptive immunity is involved in specific virus clearance. On the other hand, to achieve a successful infection, IAVs also apply multiple strategies to avoid be detected and eliminated by the host immunity. In the current review, we present a general description on recent work regarding different host cells and molecules facilitating antiviral defenses against IAV infection and how IAVs antagonize host immune responses.

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Protein arginine methyltransferase 5 mediates arginine symmetric dimethylation of influenza A virus PB2 and supports viral replication

Sun,

Tu,

Luo

et al. 2023

Journal of Medical Virology

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Influenza A virus (IAV) relies on intricate and highly coordinated associations with host factors for efficient replication and transmission. Characterization of such factors holds great significance for development of anti‐IAV drugs. Our study identified protein arginine methyltransferase 5 (PRMT5) as a novel host factor indispensable for IAV replication. Silencing PRMT5 resulted in drastic repression of IAV replication. Our findings revealed that PRMT5 interacts with each protein component of viral ribonucleoproteins (vRNPs) and promotes arginine symmetric dimethylation of polymerase basic 2 (PB2). Overexpression of PRMT5 enhanced viral polymerase activity in a dose‐dependent manner, emphasizing its role in genome transcription and replication of IAV. Moreover, analysis of PB2 protein sequences across various subtypes of IAVs demonstrated the high conservation of potential RG motifs recognized by PRMT5. Overall, our study suggests that PRMT5 supports IAV replication by facilitating viral polymerase activity by interacting with PB2 and promoting its arginine symmetric dimethylation. This study deepens our understanding of how IAV manipulates host factors to facilitate its replication and highlights the great potential of PRMT5 to serve as an anti‐IAV therapeutic target.

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The Nucleolar Protein LYAR Facilitates Ribonucleoprotein Assembly of Influenza A Virus

Cited by 22 publications

References 76 publications

LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3

LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3

Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection

Protein arginine methyltransferase 5 mediates arginine symmetric dimethylation of influenza A virus PB2 and supports viral replication

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