American Strain of Zika Virus Causes More Severe Microcephaly Than an Old Asian Strain in Neonatal Mice

Zhang, Feng; Wang, Hong Jiang; Wang, Qin; Liu, Zhong-Yu; Yuan, Ling; Huang, Xing; Li, Guanghui; Ye, Qing; Yang, Haozhen; Shi, Lei; Deng, Yong Qiang; Cheng, Qi; Xu, Zhiheng

doi:10.1016/j.ebiom.2017.10.019

Cited by 46 publications

(64 citation statements)

References 44 publications

(66 reference statements)

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“…We provide evidence for a much weaker and delayed activation of innate immune signaling by ZIKV/Brazil, a strain with a high association with CZVS. In comparison to ZIKV/Uganda and ZIKV/Brazil, viral replication of ZIKV/Cambodia, an Asian strain with less severe pathological outcomes (33), demonstrates a higher sensitivity to the antiviral action of IFN-␤. Finally, we identify RIG-I as a major PRR at early time points after ZIKV infection.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of African and Asian Lineage-Derived Zika Virus Strains Reveals Differences in Activation of and Sensitivity to Antiviral Innate Immunity

Esser-Nobis

Aarreberg

Roby

et al. 2019

J Virol

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In recent years, Asian lineage Zika virus (ZIKV) strains emerged to cause pandemic outbreaks associated with a high rate of congenital ZIKV syndrome (CZVS). The reasons for the enhanced spread and severe disease caused by newly emerging strains are not fully understood. Here we compared viral sequences, viral replication, and innate immune signaling induction of three different ZIKV strains derived from African and Asian lineages and West Nile virus, another flavivirus. We found pronounced differences in activation of innate immune signaling and inhibition of viral replication across ZIKV strains. The newly emerged Asian ZIKV strain Brazil Fortaleza 2015, which is associated with a higher rate of neurodevelopmental disorders like microcephaly, induced much weaker and delayed innate immune signaling in infected cells. However, superinfection studies to assess control of innate immune signaling induced by Sendai virus argue against an active block of IRF3 activation by the Brazilian strain of ZIKV and rather suggest an evasion of detection by host cell pattern recognition receptors. Compared to the Asian strain FSS13025 isolated in Cambodia, both ZIKV Uganda MR766 and ZIKV Brazil Fortaleza appear less sensitive to the interferon-induced antiviral response. ZIKV infection studies of cells lacking the different RIG-I-like receptors identified RIG-I as the major cytosolic pattern recognition receptor for detection of ZIKV. IMPORTANCE Zika Virus (ZIKV), discovered in 1947, is divided into African and Asian lineages. Pandemic outbreaks caused by currently emerging Asian lineage strains are accompanied by high rates of neurological disorders and exemplify the global health burden associated with this virus. Here we compared virological and innate immunological aspects of two ZIKV strains from the Asian lineage, an emerging Brazilian strain and a less-pathogenic Cambodian strain, and the prototypic African lineage ZIKV strain from Uganda. Compared to the replication of other ZIKV strains, the replication of ZIKV Brazil was less sensitive to the antiviral actions of interferon (IFN), while infection with this strain induced weaker and delayed innate immune responses in vitro. Our data suggest that ZIKV Brazil directs a passive strategy of innate immune evasion that is reminiscent of a stealth virus. Such strain-specific properties likely contribute to differential pathogenesis and should be taken into consideration when choosing virus strains for future molecular studies.

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Section: Discussionmentioning

confidence: 99%

Comparative Analysis of African and Asian Lineage-Derived Zika Virus Strains Reveals Differences in Activation of and Sensitivity to Antiviral Innate Immunity

Esser-Nobis

Aarreberg

Roby

et al. 2019

J Virol

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“…The detection of ZIKV in fetal brains of humans (73)(74)(75)(76)(77) and mice (13,(78)(79)(80) has led to the hypothesis that virus replication in the CNS causes adverse perinatal outcomes. Although ZIKV is detectable in the fetal brain (20,81), we have shown that ZIKV is undetectable in the neonatal brain (13).…”

Section: Discussionmentioning

confidence: 99%

IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection

et al. 2019

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“…DENV has four serotypes, and serotype-specific differences in clinical manifestations, including severe disease, have been reported in pediatric (37,38) as well as adult (39,40) populations. Zika virus (ZIKV), a virus closely related to dengue virus, has shown strain-dependent differences in ex vivo virulence (41), apoptosis induction capacity (42), infectivity (43), as well as disease manifestations in mouse models (44) and potentially humans (41). To the best of our knowledge, S:I ratios for DENV and ZIKV have not yet been examined by serotype and strain, respectively, in human populations.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection

Carrillo

Collado

Sánchez

et al. 2019

J Virol

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In late 2013, chikungunya virus (CHIKV) was introduced into the Americas, leading to widespread epidemics. A large epidemic caused by the Asian chikungunya virus (CHIKV) lineage occurred in Managua, Nicaragua, in 2015. Literature reviews commonly state that the proportion of inapparent CHIKV infections ranges from 3 to 28%. This study estimates the ratio of symptomatic to asymptomatic CHIKV infections and identifies risk factors of infection. In October to November 2015, 60 symptomatic CHIKV-infected children were enrolled as index cases and prospectively monitored, alongside 236 household contacts, in an index cluster study. Samples were collected upon enrollment and on day 14 or 35 and tested by realtime reverse transcription-PCR (rRT-PCR), IgM capture enzyme-linked immunosorbent assays (IgM-ELISAs), and inhibition ELISAs to detect pre-and postenrollment CHIKV infections. Of 236 household contacts, 55 (23%) had experienced previous or very recent infections, 41 (17%) had active infections at enrollment, and 21 (9%) experienced incident infections. Vehicle ownership (multivariable-adjusted risk ratio [aRR], 1.58) increased the risk of CHIKV infection, whereas Ն4 municipal trash collections/ week (aRR, 0.38) and having externally piped water (aRR, 0.52) protected against CHIKV infection. Among 63 active and incident infections, 31 (49% [95% confidence interval {CI}, 36%, 62%]) were asymptomatic, yielding a ratio of symptomatic to asymptomatic infections of 1:0.97 (95% CI, 1:0.56, 1:1.60). Although our estimate is outside the 3% to 28% range reported previously, Bayesian and simulation analyses, informed by a systematic literature search, suggested that the proportion of inapparent CHIKV infections is lineage dependent and that more inapparent infections are associated with the Asian lineage than the East/Central/South African (ECSA) lineage. Overall, these data substantially improve knowledge regarding chikungunya epidemics. IMPORTANCE Chikungunya virus (CHIKV) is an understudied threat to human health. During the 2015 chikungunya epidemic in Managua, Nicaragua, we estimated the ratio of symptomatic to asymptomatic CHIKV infections, which is important for understanding transmission dynamics and the public health impact of CHIKV. This index cluster study identified and monitored persons at risk of infection, enabling capture of asymptomatic infections. We estimated that 31 (49%) of 63 atrisk participants had asymptomatic CHIKV infections, which is significantly outside the 3% to 28% range reported in literature reviews. However, recent seroprevalence studies, including two large pediatric cohort studies in the same setting, had also found percentages of inapparent infections outside the 3% to 28% range. Bayesian and simulation analyses, informed by a systematic literature search, revealed that Downloaded from the percentage of inapparent infections in epidemic settings varies by CHIKV phylogenetic lineage. Our study quantifies and provides the first epidemiological evidence that chikungunya epidemic characteristic...

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American Strain of Zika Virus Causes More Severe Microcephaly Than an Old Asian Strain in Neonatal Mice

Cited by 46 publications

References 44 publications

Comparative Analysis of African and Asian Lineage-Derived Zika Virus Strains Reveals Differences in Activation of and Sensitivity to Antiviral Innate Immunity

Comparative Analysis of African and Asian Lineage-Derived Zika Virus Strains Reveals Differences in Activation of and Sensitivity to Antiviral Innate Immunity

IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection

Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection

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