Comparative analysis of a Thai congenital-Zika-syndrome-associated virus with a Thai Zika-fever-associated virus

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ORIGINAL ARTICLE

Comparative analysis of a Thai congenital‑Zika‑syndrome‑associated virus with a Thai Zika‑fever‑associated virus Anusara Jitsatja1 · Suwipa Ramphan1 · Ploenphit Promma1 · Atichat Kuadkitkan1 · Nitwara Wikan1 · Mongkol Uiprasertkul2 · Chayawat Phatihattakorn3 · Duncan R. Smith1  Received: 26 February 2020 / Accepted: 18 April 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020

Abstract In this study, we compared the characteristics of two strains of Zika virus (ZIKV) isolated in Thailand, one isolated from a febrile patient and one isolated from tissues of a fetus medically terminated due to congenital Zika syndrome (CZS). Replication profiles showed that the isolate from the fetal tissues replicated significantly more slowly than the fever-associated isolate in human lung A549 cells during the first 24 hours postinfection but showed a similar growth profile over longerterm infection. A much smaller difference was observed in Aedes albopictus C6/36 cells. In a quasispecies analysis, a high proportion (approximately 20%) of nonfunctional genomes was identified, caused by an adenine insertion in the prM gene. This insertion was found to be present in two Thai fever strains and as such may represent a common feature of Thai endemic ZIKV. Comparison between viral RNA copy number and viral titer showed that the isolate from fetal tissues was produced more efficiently than the fever-associated isolate. Together, these results suggest that different ZIKV isolates differ in their replication capacity, and this might contribute to the fetotropic potential of a particular strain.

Introduction Zika virus (ZIKV), a mosquito-transmitted member of the genus Flavivirus, family Flaviviridae, is the causative agent of Zika fever (ZIKF). The majority of cases of human infection with ZIKV are believed to be asymptomatic, but, where symptomatic, ZIKF normally manifests with fever, rash, headache, muscle and joint pain, and occasional Handling Editor: Zhenhai Chen. Anusara Jitsatja and Suwipa Ramphan contributed equally. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0070​5-020-04667​-7) contains supplementary material, which is available to authorized users. * Duncan R. Smith [email protected] 1



Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom, Thailand

2



Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

3

Department of Obstetrics and Gynaecology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand



conjunctivitis, as reviewed elsewhere [1]. ZIKF is generally self-limiting, but occasional cases of more-serious symptoms in adults, including Guillain-Barre syndrome [2], have been reported. Early studies identified two lineages of ZIKV, an African and an Asian lineage [3], reflecting the known distribution of the virus (reviewed in reference [4]). In 2013, the Asian lineage emerged from Southeast Asia and caused a large outbreak