Clarithromycin Inhibits Type A Seasonal Influenza Virus Infection in Human Airway Epithelial Cells

Yamaya, Mutsuo; Shinya, Kyoko; Hatachi, Yukimasa; Kubo, Hiroshi; Asada, Masanori; Yasuda, Hiroyasu; Nishimura, Hidekazu; Nagatomi, Ryoichi

doi:10.1124/jpet.109.162149

Cited by 76 publications

(73 citation statements)

References 35 publications

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“…We also reported previously that a macrolide antibiotic, clarithromycin, and L-carbocisteine inhibit seasonal influenza virus infection by reducing the expression level of its receptor SA␣2,6Gal and by reducing the number of acidic endosomes in human tracheal epithelial cells (44,45). In this study, we demonstrated that LVFX reduces the ICAM-1 expression level and slightly but significantly reduces the number of acidic endosomes.…”

Section: Discussionsupporting

confidence: 57%

Levofloxacin Inhibits Rhinovirus Infection in Primary Cultures of Human Tracheal Epithelial Cells

Yamaya

Nishimura²,

Hatachi

et al. 2012

Antimicrob Agents Chemother

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ABSTRACTRespiratory virus infections, including infections with rhinoviruses (RVs), are related to exacerbations of chronic obstructive pulmonary disease (COPD). A new quinolone antibiotic, levofloxacin (LVFX), has been used to treat bacterial infections that cause COPD exacerbations as well as bacterial infections that are secondary to viral infection in COPD patients. However, the inhibitory effects of LVFX on RV infection and RV infection-induced airway inflammation have not been studied. We examined the effects of LVFX on type 14 rhinovirus (RV14) (a major human RV) infection of human tracheal epithelial cells pretreated with LVFX. LVFX pretreatment reduced the RV14 titer, the level of cytokines in the supernatant, the amount of RV14 RNA in the cells after RV14 infection, and the cells' susceptibility to RV14 infection. LVFX pretreatment decreased the mRNA level of intercellular adhesion molecule 1 (ICAM-1), a receptor for RV14, in the cells and the concentration of the soluble form of ICAM-1 in the supernatant before RV14 infection. LVFX pretreatment also decreased the number and the fluorescence intensity of the acidic endosomes from which RV14 RNA enters the cytoplasm. LVFX pretreatment inhibited the activation of nuclear factor κB proteins, including p50 and p65, in nuclear extracts. LVFX pretreatment did not reduce the titers of RV2 (a minor human RV) but reduced the titers of RV15 (a major human RV). These results suggest that LVFX inhibits major-group rhinovirus infections in part by reducing ICAM-1 expression levels and the number of acidic endosomes. LVFX may also modulate airway inflammation in rhinoviral infections.

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Section: Discussionsupporting

confidence: 57%

Levofloxacin Inhibits Rhinovirus Infection in Primary Cultures of Human Tracheal Epithelial Cells

Yamaya

Nishimura²,

Hatachi

et al. 2012

Antimicrob Agents Chemother

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“…DAS181 is currently in Phase II development (27). Clarithromycin, a macrolide antibiotic used to treat tonsillitis and pharyngitis, has potential as an influenza therapeutic; it reduces the expression of sialic acid receptors on the surface of airway epithelial cells and decreases the number of acidic endosomes in the cell, reducing viral endocytosis (31).…”

Section: Discussionmentioning

confidence: 99%

Prevention of influenza by targeting host receptors using engineered proteins

Connaris

Govorkova

Ligertwood

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance We have developed a new class of host-targeted biologics to prevent influenza by engineering multivalent carbohydrate-binding modules that bind with high affinity to sialic acid, the critical component of the influenza virus cell surface receptor. Mouse studies reveal a remarkable efficacy: a single 1-μg dose of the lead biologic given 7 d before a lethal challenge with 2009 pandemic H1N1 influenza virus provides complete protection. This new approach has the potential to be a front-line defense against any current and future influenza virus, overcoming viral escape to vaccines and antivirals. In addition, the biologics may have broader application against other respiratory pathogens.

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“…Of interest, we have also reported that 75% of patients treated with the combination of CAM and OSV showed increases in S-IgA production to levels similar to those seen in patients treated with CAM alone (37). Others have also reported that CAM acted on the viral replication cycles, resulting in inhibition of progeny virus production in vitro (25,26), and modulated airway inflammation in IAV infection by reduction of the viral receptor, sialic acid with an ␣2,6 linkage on the airway epithelial cells, through inhibition of nuclear factor kappa B (NF-B) expression and increase in intraendosomal pH (45).…”

mentioning

confidence: 93%

“…At days 8 and 12 after infection, nasal washes (NWs), bronchoalveolar fluids (BALF), and plasma were collected as described previously (27,45) and subjected to enzyme-linked immunosorbent assay (ELISA) to determine anti IAV-specific S-IgA and IgG levels (27,33,39). Mononuclear cells isolated from the MeLNs, lungs, NPs, and spleen were subjected to an enzyme-linked immunosorbent spot (ELISPOT) assay to determine the numbers of IgA and IgG antibody (Ab)-forming cells (AFCs), as described previously (15,17,39).…”

Section: Methodsmentioning

confidence: 99%

Oral Clarithromycin Enhances Airway Immunoglobulin A (IgA) Immunity through Induction of IgA Class Switching Recombination and B-Cell-Activating Factor of the Tumor Necrosis Factor Family Molecule on Mucosal Dendritic Cells in Mice Infected with Influenza A Virus

Takahashi

Kataoka

Indalao

et al. 2012

J Virol

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We previously reported that the macrolide antibiotic clarithromycin (CAM) enhanced the mucosal immune response in pediatric influenza, particularly in children treated with the antiviral neuraminidase inhibitor oseltamivir (OSV) with low production of mucosal antiviral secretory IgA (S-IgA). The aims of the present study were to confirm the effects of CAM on S-IgA immune responses, by using influenza A virus (IAV) H1N1-infected mice treated with or without OSV, and to determine the molecular mechanisms responsible for the induction of mucosal IgA class switching recombination in IAV-infected CAM-treated mice. The anti-IAV S-IgA responses and expression levels of IgA class switching recombination-associated molecules were examined in bronchus-lymphoid tissues and spleens of infected mice. We also assessed neutralization activities of S-IgA against IAV. Data show that CAM enhanced anti-IAV S-IgA induction in the airway of infected mice and restored the attenuated antiviral S-IgA levels in OSV-treated mice to the levels in the vehicle-treated mice. The expression levels of B-cell-activating factor of the tumor necrosis factor family (BAFF) molecule on mucosal dendritic cells as well as those of activation-induced cytidine deaminase and Iμ-Cα transcripts on B cells were enhanced by CAM, compared with the levels without CAM treatment, but CAM had no effect on the expression of the BAFF receptor on B cells. Enhancement by CAM of neutralization activities of airway S-IgA against IAV in vitro and reinfected mice was observed. This study identifies that CAM enhances S-IgA production and neutralizing activities through the induction of IgA class switching recombination and upregulation of BAFF molecules in mucosal dendritic cells in IAV-infected mice.

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Clarithromycin Inhibits Type A Seasonal Influenza Virus Infection in Human Airway Epithelial Cells

Abstract: Human influenza viruses attach to sialic acid with an

Cited by 76 publications

References 35 publications

Levofloxacin Inhibits Rhinovirus Infection in Primary Cultures of Human Tracheal Epithelial Cells

Levofloxacin Inhibits Rhinovirus Infection in Primary Cultures of Human Tracheal Epithelial Cells

Prevention of influenza by targeting host receptors using engineered proteins

Oral Clarithromycin Enhances Airway Immunoglobulin A (IgA) Immunity through Induction of IgA Class Switching Recombination and B-Cell-Activating Factor of the Tumor Necrosis Factor Family Molecule on Mucosal Dendritic Cells in Mice Infected with Influenza A Virus

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