The inducible amphisome isolates viral hemagglutinin and defends against influenza A virus infection

Omi, Jumpei; Watanabe-Takahashi, Miho; Igai, Katsura; Shimizu, Eihan; Tseng, Ching Yi; Miyasaka, Tomohiro; Waku, Tsuyoshi; Hama, Shinichiro; Nakanishi, Rieka; Nishino, Yuri; Miyazawa, Atsuo; Natori, Yasuhiro; Yamashita, Makoto; Nishikawa, Kiyotaka

doi:10.1038/s41467-019-13974-w

Cited by 16 publications

(10 citation statements)

References 65 publications

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“…2d ). Notably, these values indicate that LME-tet functions based on the clustering effect, a phenomenon by which multivalent interactions between two molecules with multi-subunit or oligomeric structure markedly increase the binding affinity as compared to a 1:1 monomeric interaction 23 , 27 , 29 . The relatively higher binding affinity to Aβ42 vs. Aβ40 may thus reflect its propensity to aggregate, thus exaggerating the clustering effect.…”

Section: Resultsmentioning

confidence: 99%

A tailored tetravalent peptide displays dual functions to inhibit amyloid β production and aggregation

et al. 2023

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Inhibition of amyloid-β peptide (Aβ) accumulation in the brain is a promising approach for treatment of Alzheimer’s disease (AD). Aβ is produced by β-secretase and γ-secretase in endosomes via sequential proteolysis of amyloid precursor protein (APP). Aβ and APP have a common feature to readily cluster to form multimers. Here, using multivalent peptide library screens, we identified a tetravalent peptide, LME-tet, which binds APP and Aβ via multivalent interactions. In cells, LME-tet-bound APP in the plasma membrane is transported to endosomes, blocking Aβ production through specific inhibition of β-cleavage, but not γ-cleavage. LME-tet further suppresses Aβ aggregation by blocking formation of the β-sheet conformation. Inhibitory effects are not observed with a monomeric peptide, emphasizing the significance of multivalent interactions for mediating these activities. Critically, LME-tet efficiently reduces Aβ levels in the brain of AD model mice, suggesting it may hold promise for treatment of AD.

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Section: Resultsmentioning

confidence: 99%

A tailored tetravalent peptide displays dual functions to inhibit amyloid β production and aggregation

et al. 2023

Self Cite

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“…Furthermore, transmission electron microscopy revealed a decrease in the number of autophagosomes after treatment with sh- LAMTOR1 ( Supplementary Figure S3B available at Carcinogenesis Online). In response to stress, cells initiate endocytosis and autophagy to maintain cellular homeostasis ( 30 , 31 ). This leads to the formation of amphisomes, which are hybrid organelles that play a key role in the cross-talk between endosomes and autophagy ( 32 ).…”

Section: Resultsmentioning

confidence: 99%

LAMTOR1 degrades MHC-II via the endocytic in hepatocellular carcinoma

Wang

et al. 2022

Carcinogenesis

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Tumor cell surface antigen recognition is a major hallmark of cancer therapy, and loss of major histocompatibility complex class I (MHC-I) is the most common mechanism that impairs tumor cell surface antigen processing and expression. In addition to this, MHC-II regulates antigen presentation in CD4+ T cell immune responses involved in tumor killing by CD8+ T cells, whereas the regulation of endocytosis regulating MHC-II antigen presentation has not been reported. Therefore, the regulation of the endocytosis pathway on the expression of MHC-II surface level and anti-tumor T cell response remains to be explored. In this experiments, we found that LAMTOR1 regulates the endocytic pathway through the GTPase domain of DNM2 and triggers the formation of autophagosomes. We performed flow cytometry and western blotting analyses, which revealed that the expression of MHC-II molecules on the surface of cells is influenced by LAMTOR1 through the endocytic pathway. We showed that the expression of MHC-II molecules, which recognize CD4 + T cells on the surface of cells, was regulated by LAMTOR1 through an endocytic pathway. By co-culture experiments, we showed that CD8 +/CD4 + T cells exhibit substantially higher levels of tumor cell apoptosis than those observed when HCC cells were co-cultured with CD8 + T cells alone. This study revealed that LAMTOR1 decreases the expression levels of MHC-II on cell surfaces in order to reduce antigen expression, leading to a decrease in anti-tumor T cell responses.

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“…In fact, PVF-tet does not interact with H1 and H2, but likely does with the H0 of newly synthesized viral particles. PVF-tet is a cell-penetrating peptide, and its addition to the infected cell causes the amassment of HA in a vacuole-like structures named amphisomes [ 121 ]. A synthetic report of the most representative peptides binding the head of HA is presented in Table 2 .…”

Section: Peptides Targeting Hamentioning

confidence: 99%

Antiviral Peptides as Anti-Influenza Agents

Agamennone

Fantacuzzi

Vivenzio

et al. 2022

IJMS

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Influenza viruses represent a leading cause of high morbidity and mortality worldwide. Approaches for fighting flu are seasonal vaccines and some antiviral drugs. The development of the seasonal flu vaccine requires a great deal of effort, as careful studies are needed to select the strains to be included in each year’s vaccine. Antiviral drugs available against Influenza virus infections have certain limitations due to the increased resistance rate and negative side effects. The highly mutative nature of these viruses leads to the emergence of new antigenic variants, against which the urgent development of new approaches for antiviral therapy is needed. Among these approaches, one of the emerging new fields of “peptide-based therapies” against Influenza viruses is being explored and looks promising. This review describes the recent findings on the antiviral activity, mechanism of action and therapeutic capability of antiviral peptides that bind HA, NA, PB1, and M2 as a means of countering Influenza virus infection.

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The inducible amphisome isolates viral hemagglutinin and defends against influenza A virus infection

Cited by 16 publications

References 65 publications

A tailored tetravalent peptide displays dual functions to inhibit amyloid β production and aggregation

A tailored tetravalent peptide displays dual functions to inhibit amyloid β production and aggregation

LAMTOR1 degrades MHC-II via the endocytic in hepatocellular carcinoma

Antiviral Peptides as Anti-Influenza Agents

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