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Article: Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs

TitleDifferential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs
Authors
Issue Date2016
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emi/marketing/index.html
Citation
Emerging Microbes & Infections, 2016, v. 5, article no. e93 How to Cite?
AbstractZika virus (ZIKV) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to-human transmission. Although the pathogenesis of ZIKV-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of ZIKV remain unanswered. We systematically characterized the differential cell line susceptibility of 18 human and 15 nonhuman cell lines to two ZIKV isolates (human and primate) and dengue virus type 2 (DENV-2). Productive ZIKV replication (⩾2 log increase in viral load, ZIKV nonstructural protein-1 (NS1) protein expression and cytopathic effects (CPE)) was found in the placental (JEG-3), neuronal (SF268), muscle (RD), retinal (ARPE19), pulmonary (Hep-2 and HFL), colonic (Caco-2),and hepatic (Huh-7) cell lines. These findings helped to explain the trans-placental transmission and other clinical manifestations of ZIKV. Notably, the prostatic (LNCaP), testicular (833KE) and renal (HEK) cell lines showed increased ZIKV load and/or NS1 protein expression without inducing CPE, suggesting their potential roles in sexual transmission with persistent viral replication at these anatomical sites. Comparatively, none of the placental and genital tract cell lines allowed efficient DENV-2 replication. Among the nonhuman cell lines, nonhuman primate (Vero and LLC-MK2), pig (PK-15), rabbit (RK-13), hamster (BHK21) and chicken (DF-1) cell lines supported productive ZIKV replication. These animal species may be important reservoirs and/or potential animal models for ZIKV. The findings in our study help to explain the viral shedding pattern, transmission and pathogenesis of the rapidly disseminating ZIKV, and are useful for optimizing laboratory diagnostics and studies on the pathogenesis and counter-measures of ZIKV.
Persistent Identifierhttp://hdl.handle.net/10722/233667
ISSN
2018 Impact Factor: 6.212
2015 SCImago Journal Rankings: 1.774
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, JFW-
dc.contributor.authorYip, CY-
dc.contributor.authorTsang, OL-
dc.contributor.authorTee, KM-
dc.contributor.authorCai, J-
dc.contributor.authorChik, KKH-
dc.contributor.authorZhu, Z-
dc.contributor.authorChan, CS-
dc.contributor.authorCHOI, KY-
dc.contributor.authorSridhar, S-
dc.contributor.authorZhang, J-
dc.contributor.authorLu, G-
dc.contributor.authorChiu, K-
dc.contributor.authorLo, ACY-
dc.contributor.authorTsao, GSW-
dc.contributor.authorKok, KH-
dc.contributor.authorJin, D-
dc.contributor.authorChan, KH-
dc.contributor.authorYuen, KY-
dc.date.accessioned2016-09-20T05:38:20Z-
dc.date.available2016-09-20T05:38:20Z-
dc.date.issued2016-
dc.identifier.citationEmerging Microbes & Infections, 2016, v. 5, article no. e93-
dc.identifier.issn2222-1751-
dc.identifier.urihttp://hdl.handle.net/10722/233667-
dc.description.abstractZika virus (ZIKV) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to-human transmission. Although the pathogenesis of ZIKV-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of ZIKV remain unanswered. We systematically characterized the differential cell line susceptibility of 18 human and 15 nonhuman cell lines to two ZIKV isolates (human and primate) and dengue virus type 2 (DENV-2). Productive ZIKV replication (⩾2 log increase in viral load, ZIKV nonstructural protein-1 (NS1) protein expression and cytopathic effects (CPE)) was found in the placental (JEG-3), neuronal (SF268), muscle (RD), retinal (ARPE19), pulmonary (Hep-2 and HFL), colonic (Caco-2),and hepatic (Huh-7) cell lines. These findings helped to explain the trans-placental transmission and other clinical manifestations of ZIKV. Notably, the prostatic (LNCaP), testicular (833KE) and renal (HEK) cell lines showed increased ZIKV load and/or NS1 protein expression without inducing CPE, suggesting their potential roles in sexual transmission with persistent viral replication at these anatomical sites. Comparatively, none of the placental and genital tract cell lines allowed efficient DENV-2 replication. Among the nonhuman cell lines, nonhuman primate (Vero and LLC-MK2), pig (PK-15), rabbit (RK-13), hamster (BHK21) and chicken (DF-1) cell lines supported productive ZIKV replication. These animal species may be important reservoirs and/or potential animal models for ZIKV. The findings in our study help to explain the viral shedding pattern, transmission and pathogenesis of the rapidly disseminating ZIKV, and are useful for optimizing laboratory diagnostics and studies on the pathogenesis and counter-measures of ZIKV.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emi/marketing/index.html-
dc.relation.ispartofEmerging Microbes & Infections-
dc.titleDifferential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs-
dc.typeArticle-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailYip, CY: yipcyril@hku.hk-
dc.identifier.emailTsang, OL: oltsang@hku.hk-
dc.identifier.emailCai, J: caijuice@hku.hk-
dc.identifier.emailZhu, Z: zzonezz@hku.hk-
dc.identifier.emailChan, CS: cschan@hku.hk-
dc.identifier.emailSridhar, S: sid8998@hku.hk-
dc.identifier.emailZhang, J: zhangajx@hkucc.hku.hk-
dc.identifier.emailChiu, K: datwai@hkucc.hku.hk-
dc.identifier.emailLo, ACY: amylo@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityYip, CY=rp01721-
dc.identifier.authorityZhang, J=rp00413-
dc.identifier.authorityChiu, K=rp01973-
dc.identifier.authorityLo, ACY=rp00425-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityJin, D=rp00452-
dc.identifier.authorityChan, KH=rp01921-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/emi.2016.99-
dc.identifier.pmcidPMC5034105-
dc.identifier.hkuros265279-
dc.identifier.volume5-
dc.identifier.spagearticle no. e93-
dc.identifier.epagearticle no. e93-
dc.identifier.isiWOS:000383401900001-
dc.publisher.placeUnited Kingdom-

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