Human Respiratory Syncytial Virus NS2 Protein Induces Autophagy by Modulating Beclin1 Protein Stabilization and ISGylation

Chiok, Kim; Pokharel, Swechha M.; Mohanty, Indira; Miller, Lindsay Grace; Gao, Shou‐Jiang; Haas, Arthur; Tran, Kim C.; Teng, Michael N.; Bose, Santanu

doi:10.1128/mbio.03528-21

Cited by 21 publications

(17 citation statements)

References 51 publications

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“…These findings were further consolidated in recent reports, which identified Respiratory syncytial virus (RSV) NS2 as an antagonist of this pathway. NS2 was found to promote pro-viral autophagy by stabilising Beclin1 and preventing its ISGylation [50]. These data on the negative regulation of autophagy are in line with previous studies on IFNβ-induced ISGylation of Trim21.…”

Section: Regulation Of Autophagysupporting

confidence: 90%

ISG15 driven cellular responses to virus infection

Munnur

Banducci-Karp

Sanyal

2022

Biochemical Society Transactions

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One of the hallmarks of antiviral responses to infection is the production of interferons and subsequently of interferon stimulated genes. Interferon stimulated gene 15 (ISG15) is among the earliest and most abundant proteins induced upon interferon signalling, encompassing versatile functions in host immunity. ISG15 is a ubiquitin like modifier that can be conjugated to substrates in a process analogous to ubiquitylation and referred to as ISGylation. The free unconjugated form can either exist intracellularly or be secreted to function as a cytokine. Interestingly, ISG15 has been reported to be both advantageous and detrimental to the development of immunopathology during infection. This review describes recent findings on the role of ISG15 in antiviral responses in human infection models, with a particular emphasis on autophagy, inflammatory responses and cellular metabolism combined with viral strategies of counteracting them. The field of ISGylation has steadily gained momentum; however much of the previous studies of virus infections conducted in mouse models are in sharp contrast with recent findings in human cells, underscoring the need to summarise our current understanding of its potential antiviral function in humans and identify knowledge gaps which need to be addressed in future studies.

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Section: Regulation Of Autophagysupporting

confidence: 90%

ISG15 driven cellular responses to virus infection

Munnur

Banducci-Karp

Sanyal

2022

Biochemical Society Transactions

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“…However, the alteration of Beclin 1 protein status along with its localization in parasite containing compartment throughout Leishmania infection in infected macrophages is certainly a new finding. Previously, respiratory syncytial virus (RSV) was found to induce Beclin 1 protein level by inhibiting its degradation to drive enhanced autophagy (Chiok et al, 2022). In fact, increased phosphorylation of Beclin 1 at early time point has been reported during L. donovani infection (Pitale et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

A novel role of macrophage PIST protein in regulatingLeishmania majorinfection

Banerjee

Gadpayle

Das

et al. 2023

Preprint

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PDZ protein interacting specifically with Tc10 or PIST is a mammalian trans-Golgi resident protein that regulates subcellular sorting of plasma membrane receptors. PIST has recently been found to play an important role in regulating viral pathogenesis. Alteration in PIST expression is linked to the reprogramming of cell surface receptors which is crucial in determining herpes simplex virus1 infection. In this context, PIST is crucial in triggering autophagy via Beclin 1 -PI3KC3 pathway. However, there is complete lack in our knowledge on the role of this protein in any parasitic infection. Leishmania parasites infect their host macrophage cells via phagocytosis and their survival within the parasitophorous compartment has recently been found to be dependent on host autophagy by a yet to be identified mechanism. Using Leishmania major (L. major)- macrophage infection model system we, for the first-time report here that in infected macrophages Golgi resident PIST protein migrates towards the parasite containing compartment. We have also found that PIST associates with Beclin 1, however, not with LC3 within the L. major parasite containing compartment of infected macrophages. Further, we performed genetic ablation of PIST by siRNA and observed that knockdown of macrophage PIST in turn helps in parasite replication. Contrary to this, overexpression of PIST in macrophages restricted the multiplication of L. major. Collectively, our study for the first time reveals that PIST is essential in regulating intracellular parasite, L. major infection within macrophage cells.

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“…Specifically, the deletion of ISG15 leads to impaired recruitment of p62, NDP52, and LC3 in parasitophorous vacuoles (PV), resulting in interferon-induced autophagy damage. And ISGylation can further inhibit autophagy by reducing the stability of the proautophagy mediator Beclin1 to inhibit its activity [ 56 , 61 , 62 ] ( Figure 3 ).…”

Section: Isgylation In Cancermentioning

confidence: 99%

“…In addition, Xi et al demonstrated that the cancer-promoting effect of USP18 may be achieved through the control of fatty acid metabolism in lung cancer [ 94 ] ( Figure 6 ). Notably, some other studies have shown that USP18 has a strong tumor-promoting effect, indicating that USP18 functions through other important pathways besides de-ISGylase [ 62 , 78 ].…”

Section: Isgylation In Cancermentioning

confidence: 99%

The Functional Roles of ISG15/ISGylation in Cancer

Yuan

Qin

et al. 2023

Molecules

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The protein ISG15 encoded by interferon-stimulated gene (ISG) 15 is the first identified member of the ubiquitin-like protein family and exists in the form of monomers and conjugated complexes. Like ubiquitin, ISG15 can mediate an ubiquitin-like modification by covalently modifying other proteins, known as ISGylation. There is growing evidence showing that both the free and conjugated ISG15 are involved in multiple key cellular processes, including autophagy, exosome secretion, DNA repair, immune regulation, and cancer occurrence and progression. In this review, we aim to further clarify the function of ISG15 and ISGylation in cancer, demonstrate the important relationship between ISG15/ISGylation and cancer, and emphasize new insights into the different roles of ISG15/ISGylation in cancer progression. This review may contribute to therapeutic intervention in cancer. However, due to the limitations of current research, the regulation of ISG15/ISGylation on cancer progression is not completely clear, thus further comprehensive and sufficient correlation studies are still needed.

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Human Respiratory Syncytial Virus NS2 Protein Induces Autophagy by Modulating Beclin1 Protein Stabilization and ISGylation

Cited by 21 publications

References 51 publications

ISG15 driven cellular responses to virus infection

ISG15 driven cellular responses to virus infection

A novel role of macrophage PIST protein in regulatingLeishmania majorinfection

The Functional Roles of ISG15/ISGylation in Cancer

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