Zika and the Risk of Microcephaly

Johansson, Michael A.; Mier-y-Terán-Romero, Luis; Reefhuis, Jennita; Gilboa, Suzanne M.; Hills, Susan L.

doi:10.1056/nejmp1605367

Cited by 406 publications

(330 citation statements)

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“…Given the high potency and in vivo efficacy shown in this study, these antibodies, developed in wild type or their LALA versions produced in wild-type version or in LALA version so as to avoid possible enhancement, could be used in prophylactic or therapeutic settings to prevent congenital ZIKV infection in pregnant women living in high-risk areas (37). ZIKV in A129 mice Fig.…”

mentioning

confidence: 98%

Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

Stettler

Beltramello

Espinosa

et al. 2016

Science

701

893

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Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory lymphocytes from ZIKV-infected patients, we dissected ZIKV-specific and DENV-cross-reactive immune responses. Antibodies to nonstructural protein 1 (NS1) were largely ZIKV-specific and were used to develop a serological diagnostic tool. In contrast, antibodies against E protein domain I/II (EDI/II) were cross-reactive and, although poorly neutralizing, potently enhanced ZIKV and DENV infection in vitro and lethally enhanced DENVdisease in mice. Memory Tcells against NS1 or E proteins were poorly cross-reactive, even in donors preexposed to DENV. The most potent neutralizing antibodies were ZIKV-specific and targeted EDIII or quaternary epitopes on infectious virus. An EDIII-specific antibody protected mice from lethal ZIKV infection, illustrating the potential for antibody-based therapy.A fter its introduction into Brazil in 2015, Zika virus (ZIKV) has spread rapidly, and in February 2016, the World Health Organization (WHO) declared it a Public Health Emergency of International Concern (1-3). The main route of ZIKV infection is through bites by Aedes mosquitos, but the virus may also be sexually (4) and vertically transmitted (5). Although most of the ZIKV infections are asymptomatic or cause only mild symptoms, there is evidence that ZIKV infection can lead to neurological complications, such as Guillain-Barré syndrome in adults (6) and congenital birth defects, including microcephaly in the developing fetus (5,7,8), likely through its ability to infect human neural progenitor cells (9).Whereas flavivirus envelope (E) proteins mediate fusion and are the main target of neutralizing antibodies, the nonstructural protein 1 (NS1) is secreted by infected cells and is involved in immune evasion and pathogenesis (10). Two recent studies showed a high level of structural similarity between the E protein of ZIKV and that of other flaviviruses-such as dengue virus (DENV), yellow fever virus (YFV), and West Nile virus (WNV)-but also revealed distinct features that may be related to the ZIKV neurotropism (11,12). Similarly, the structural analysis of ZIKV NS1 revealed conserved features with NS1 of other flaviviruses, although with different electrostatic characteristics (13).A phenomenon that is characteristic of certain flaviviruses is the disease-enhancing activity of cross-reactive antibodies elicited by previous infections by heterologous viruses, termed antibodydependent enhancement (ADE). In the case of DENV, for which four serotypes are known, there is epidemiological evidence that a primary infection protects from reinfection with the same serotype but represents a risk factor for the development of severe disease upon reinfection with a different serotype (14). The exacerbated disease is triggered by E-and prM-specific antibodies that fail to neutralize the incoming virus but instead enhance its capture by Fc receptor-expressing (FcR + ) cells, leading to enhanced vi...

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mentioning

confidence: 98%

Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

Stettler

Beltramello

Espinosa

et al. 2016

Science

701

893

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“…The overlap of confirmed cases with the river basins of RN [22,23] (Figure 2 These results must be comprehended in light of the fact that the epidemiology of this disease is not fully understood. It is important to note that not all the pregnant women affected by Zika in the first trimester of pregnancy had microcephalic or malformed babies [6][7][8], that the cases of Zika related microcephaly are more frequent in Brazil than in others affected countries [10] and that inside the country the disease is more prevalent in the Northeast region and in low-income families [1,12]. This set of asymmetries makes ZKV apparently an etiologic agent dependent on another factor to express its most harmful complication, [7,8,12].…”

Section: Discussionmentioning

confidence: 99%

“…It is not clear, for instance, why only the smallest part of mothers who had Zika in the first trimester of pregnancy gave birth to babies affected by this complication [6][7][8]. Brazil is also the country where microcephaly is more frequent considering the reported cases of Zika [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…Brazil is also the country where microcephaly is more frequent considering the reported cases of Zika [9,10]. The predominance of microcephaly in the Northeastern region, its higher prevalence in small towns and its greater frequency in low-income children, points to other possible intervening factors [7,8] and begins to create doubts about the genesis of the problems as an isolated action of the ZKV, showing the epidemic is not entirely resolved concerning the etiological point of view [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Livestock and microcephaly, traces of an association?

Andrade

2016

Preprint

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“…The prevalence of microcephaly due to ZIKV infection in the first trimester of pregnancy ranges from 0.88% to 13.2% (50). According to WHO reports, ZIKV-related microcephaly occurs if the mother has ZIKV infection during pregnancy and the amniotic fluid test can detect ZIKV in PCR (51).…”

Section: Intrauterine and Congenital Infectionmentioning

confidence: 99%

Zika Virus, Congenital Infection, and Neurologic Manifestations in Children: A Narrative Review

Karimi

Razavi

2017

J Pediatr Rev

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Context: Zika virus (ZIKV) is an arbovirus of the family Flaviviridae. This virus, which is transmitted by mosquitoes, usually affects children and causes self-limited diseases, associated with fever, maculopapular rash, conjunctivitis, arthralgia, and myalgia. There is a significant relationship between ZIKV infection and central nervous system disorders in infants. In this study, we aimed to review neurologic manifestations of ZIKV infection in infants. Evidence Acquisition: We searched the following Mesh terms in scientific databases: "Zika virus", "infants", "children", "neurologic manifestations", and "congenital infection". Electronic databases including Google Scholar, Science Direct, PubMed, Web of Science, Scientific Information Database, and Scopus were searched from 2000 to 2016. Results:The literature review showed a probable relationship between ZIKV infection and prevalence of microcephaly in newborns. Besides microcephaly, other central nervous system abnormalities included abnormal gyral arrangement, decreased brain parenchymal volume, cortical atrophy and malformation, cerebellar hypoplasia, and delayed myelination of the brain stem. Conclusions: Vertical transmission of ZIKV in pregnant women is associated with intrauterine infection and brain malformations in the developing fetus, including microcephaly, calcification, cortical displacement, ventriculomegaly, and white-matter abnormalities.

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Zika and the Risk of Microcephaly

Cited by 406 publications

References 5 publications

Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

Livestock and microcephaly, traces of an association?

Zika Virus, Congenital Infection, and Neurologic Manifestations in Children: A Narrative Review

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