Azithromycin Protects against Zika Virus Infection by Upregulating Virus-Induced Type I and III Interferon Responses

被引：60

作者：

Li, Chunfeng ^{[1
,2
,3
,4
]}

Zu, Shulong ^{[5
,6
]}

Deng, Yong-Qiang ^{[3
]}

Li, Dapei ^{[1
,2
]}

Parvatiyar, Kislay ^{[7
,11
]}

Quanquin, Natalie ^{[7
]}

Shang, Jingzhe ^{[1
,2
]}

Sun, Nina ^{[5
,6
]}

Su, Jiaqi ^{[6
,8
]}

Liu, Zhenyang ^{[6
,8
]}

Wang, Min ^{[6
,8
]}

Aliyari, Saba R. ^{[7
]}

Li, Xiao-Feng ^{[3
]}

Wu, Aiping ^{[1
,2
]}

Ma, Feng ^{[1
,2
]}

Shi, Yi ^{[6
,8
]}

Nielsen-Saines, Karin ^{[9
]}

Jung, Jae U. ^{[10
]}

Qin, Frank Xiao-Feng ^{[1
,2
]}

Qin, Cheng-Feng ^{[3
]}

Cheng, Genhong ^{[7
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Basic Med Sci, Ctr Syst Med, Beijing, Peoples R China

[2] Suzhou Inst Syst Med, Suzhou, Jiangsu, Peoples R China

[3] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Dept Virol, Beijing, Peoples R China

[4] Stanford Univ, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA

[5] Chinese Acad Sci, Inst Biophys, CAS Key Lab Infect & Immun, Beijing, Peoples R China

[6] Univ Chinese Acad Sci, Beijing, Peoples R China

[7] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[8] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China

[9] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Pediat Infect Dis, Los Angeles, CA 90095 USA

[10] Univ Southern Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90007 USA

[11] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2019年 / 63卷 / 12期

基金：

中国国家自然科学基金;

关键词：

FDA-approved drug; azithromycin; Zika virus; type I and III interferon responses; antibiotics; antiviral agents; innate immunity; interferons; RNA VIRUSES; RIG-I; SPECTRUM; DRUG; MDA5; IDENTIFICATION; TRANSMISSION; INHIBITORS; SCREEN; CELLS;

D O I：

10.1128/AAC.00394-19

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Here, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle. In addition, AZM upregulates the expression of host type I and III interferons and several of their downstream interferon-stimulated genes in response to ZIKV infection. In particular, we found that AZM upregulated the expression of MDA5 and RIG-I (pathogen recognition receptors induced by ZIKV infection) and increased the levels of phosphorylated TBK1 and IRF3. Interestingly, AZM treatment upregulated the phosphorylation of TBK1 without inducing the phosphorylation of IRF3 by itself. These findings highlight the potential use of AZM as a broad antiviral agent to combat viral infection and to prevent devastating ZIKV-associated clinical outcomes, such as congenital microcephaly.

引用

页数：14

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