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Zika virus and the nonmicrocephalic fetus: why we should still worry

Published:August 29, 2018DOI:https://doi.org/10.1016/j.ajog.2018.08.035
      Zika virus is a mosquito-transmitted flavivirus and was first linked to congenital microcephaly caused by a large outbreak in northeastern Brazil. Although the Zika virus epidemic is now in decline, pregnancies in large parts of the Americas remain at risk because of ongoing transmission and the potential for new outbreaks. This review presents why Zika virus is still a complex and worrisome public health problem with an expanding spectrum of birth defects and how Zika virus and related viruses evade the immune response to injure the fetus. Recent reports indicate that the spectrum of fetal brain and other anomalies associated with Zika virus exposure is broader and more complex than microcephaly alone and includes subtle fetal brain and ocular injuries; thus, the ability to prenatally diagnose fetal injury associated with Zika virus infection remains limited. New studies indicate that Zika virus imparts disproportionate effects on fetal growth with an unusual femur-sparing profile, potentially providing a new approach to identify viral injury to the fetus. Studies to determine the limitations of prenatal and postnatal testing for detection of Zika virus–associated birth defects and long-term neurocognitive deficits are needed to better guide women with a possible infectious exposure. It is also imperative that we investigate why the Zika virus is so adept at infecting the placenta and the fetal brain to better predict other viruses with similar capabilities that may give rise to new epidemics. The efficiency with which the Zika virus evades the early immune response to enable infection of the mother, placenta, and fetus is likely critical for understanding why the infection may either be fulminant or limited. Furthermore, studies suggest that several emerging and related viruses may also cause birth defects, including West Nile virus, which is endemic in many parts of the United States. With mosquito-borne diseases increasing worldwide, there remains an urgent need to better understand the pathogenesis of the Zika virus and related viruses to protect pregnancies and child health.

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      References

        • Kleber de Oliveira W.
        • Cortez-Escalante J.
        • et al.
        Increase in reported prevalence of microcephaly in infants born to women living in areas with confirmed Zika Virus transmission during the first trimester of pregnancy—Brazil, 2015.
        MMWR Morb Mortal Wkly Rep. 2016; 65: 242-247
        • Gulland A.
        Zika virus is a global public health emergency, declares WHO.
        BMJ. 2016; 352: i657
        • Melo A.S.
        • Aguiar R.S.
        • Amorim M.M.
        • et al.
        Congenital Zika virus infection: beyond neonatal microcephaly.
        JAMA Neurol. 2016; 73: 1407-1416
        • Rice M.E.
        • Galang R.R.
        • Roth N.M.
        • et al.
        Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection—US territories and freely associated states, 2018.
        MMWR Morb Mortal Wkly Rep. 2018; 67: 858-867
        • Aragao M.
        • Holanda A.C.
        • Brainer-Lima A.M.
        • et al.
        Nonmicrocephalic infants with congenital Zika syndrome suspected only after neuroimaging evaluation compared with those with microcephaly at birth and postnatally: how large is the Zika virus “iceberg”?.
        AJNR Am J Neuroradiol. 2017; 38: 1427-1434
        • Shao Q.
        • Herrlinger S.
        • Yang S.L.
        • et al.
        Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage.
        Development. 2016; 143: 4127-4136
        • van der Linden V.
        • Pessoa A.
        • Dobyns W.
        • et al.
        Description of 13 infants born during October 2015–January 2016 with congenital Zika virus infection without microcephaly at birth—Brazil.
        MMWR Morb Mortal Wkly Rep. 2016; 65: 1343-1348
        • Adams Waldorf K.M.
        • Nelson B.R.
        • et al.
        Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.
        Nat Med. 2018; 24: 368-374
        • Qian X.
        • Nguyen H.N.
        • Song M.M.
        • et al.
        Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure.
        Cell. 2016; 165: 1238-1254
        • Tang H.
        • Hammack C.
        • Ogden S.C.
        • et al.
        Zika virus infects human cortical neural progenitors and attenuates their growth.
        Cell Stem Cell. 2016; 18: 587-590
        • Tabata T.
        • Petitt M.
        • Puerta-Guardo H.
        • et al.
        Zika virus targets different primary human placental cells, suggesting two routes for vertical transmission.
        Cell Host Microbe. 2016; 20: 155-166
        • El Costa H.
        • Gouilly J.
        • Mansuy J.M.
        • et al.
        ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy.
        Sci Rep. 2016; 6: 35296
        • Jurado K.A.
        • Simoni M.K.
        • Tang Z.
        • et al.
        Zika virus productively infects primary human placenta-specific macrophages.
        JCI Insight. 2016; 1
        • Soares de Oliveira-Szejnfeld P.
        • Levine D.
        • Melo A.S.
        • et al.
        Congenital brain abnormalities and Zika virus: what the radiologist can expect to see prenatally and postnatally.
        Radiology. 2016; 281: 203-218
        • Schuler-Faccini L.
        • Ribeiro E.M.
        • Feitosa I.M.
        • et al.
        Possible association between Zika virus infection and microcephaly—Brazil, 2015.
        MMWR Morb Mortal Wkly Rep. 2016; 65: 59-62
        • Moura da Silva A.A.
        • Ganz J.S.
        • Sousa P.D.
        • et al.
        Early growth and neurologic outcomes of infants with probable congenital Zika virus syndrome.
        Emerg Infect Dis. 2016; 22: 1953-1956
        • de Fatima Vasco Aragao M.
        • van der Linden V.
        • Brainer-Lima A.M.
        • et al.
        Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study.
        BMJ. 2016; 353: i1901
        • Aragao M.
        • Brainer-Lima A.M.
        • Holanda A.C.
        • et al.
        Spectrum of spinal cord, spinal root, and brain MRI abnormalities in congenital Zika syndrome with and without arthrogryposis.
        AJNR Am J Neuroradiol. 2017; 38: 1045-1053
      1. Centers for Disease Control and Prevention. Zika virus, 2018. Available at: www.cdc.gov/zika. Accessed September 11, 2018.

        • Franca G.V.A.
        • Schuler-Faccini L.
        • Oliveira W.K.
        • et al.
        Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation.
        Lancet. 2016; 388: 891-897
        • Society for Maternal-Fetal Medicine Publications Committee
        Ultrasound screening for fetal microcephaly following Zika virus exposure.
        Am J Obstet Gynecol. 2016; 214: B2-B4
        • Sanz Cortes M.
        • Rivera A.M.
        • Yepez M.
        • et al.
        Clinical assessment and brain findings in a cohort of mothers, fetuses and infants infected with Zika virus.
        Am J Obstet Gynecol. 2018; 218: 440.e1-440.e3
        • Papageorghiou A.T.
        • Thilaganathan B.
        • Bilardo C.M.
        • et al.
        ISUOG interim guidance on ultrasound for Zika virus infection in pregnancy: information for healthcare professionals.
        Ultrasound Obstet Gynecol. 2016; 47: 530-532
        • Juca E.
        • Pessoa A.
        • Ribeiro E.
        • et al.
        Hydrocephalus associated to congenital Zika syndrome: does shunting improve clinical features?.
        Childs Nerv Syst. 2018; 34: 101-106
        • Papageorghiou A.T.
        • Ohuma E.O.
        • Altman D.G.
        • et al.
        International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.
        Lancet. 2014; 384: 869-879
        • Heukelbach J.
        • Werneck G.L.
        Surveillance of Zika virus infection and microcephaly in Brazil.
        Lancet. 2016; 388: 846-847
        • Hazin A.N.
        • Poretti A.
        • Turchi Martelli C.M.
        • et al.
        Computed tomographic findings in microcephaly associated with Zika virus.
        N Engl J Med. 2016; 374: 2193-2195
        • Victora C.G.
        • Schuler-Faccini L.
        • Matijasevich A.
        • Ribeiro E.
        • Pessoa A.
        • Barros F.C.
        Microcephaly in Brazil: how to interpret reported numbers?.
        Lancet. 2016; 387: 621-624
        • Eppes C.
        • Rac M.
        • Dunn J.
        • et al.
        Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic.
        Am J Obstet Gynecol. 2017; 216: 209-225
      2. Centers for Disease Control and Prevention. Guidance for laboratories testing for Zika virus infection. 2017. Available at: https://www.cdc.gov/zika/laboratories/lab-guidance.html. Accessed March 19, 2018.

        • Granger D.
        • Hilgart H.
        • Misner L.
        • et al.
        Serologic testing for Zika virus: comparison of three Zika virus IgM-screening enzyme-linked immunosorbent assays and initial laboratory experiences.
        J Clin Microbiol. 2017; 55: 2127-2136
        • Felix A.C.
        • Souza N.C.S.
        • Figueiredo W.M.
        • et al.
        Cross reactivity of commercial anti-dengue immunoassays in patients with acute Zika virus infection.
        J Med Virol. 2017; 89: 1477-1479
        • Reynolds M.R.
        • Jones A.M.
        • Petersen E.E.
        • et al.
        Vital signs: update on Zika virus–associated birth defects and evaluation of all US infants with congenital Zika virus exposure—US Zika Pregnancy Registry, 2016.
        MMWR Morb Mortal Wkly Rep. 2017; 66: 366-373
        • Zin A.A.
        • Tsui I.
        • Rossetto J.
        • et al.
        Screening criteria for ophthalmic manifestations of congenital Zika virus infection.
        JAMA Pediatr. 2017; 171: 847-854
        • Shiu C.
        • Starker R.
        • Kwal J.
        • et al.
        Zika virus testing and outcomes during pregnancy, Florida, USA, 2016.
        Emerg Infect Dis. 2018; 24: 1-8
        • Sohan K.
        • Cyrus C.A.
        Ultrasonographic observations of the fetal brain in the first 100 pregnant women with Zika virus infection in Trinidad and Tobago.
        Int J Gynaecol Obstet. 2017; 139: 278-283
        • Petribu N.C.L.
        • Aragao M.F.V.
        • van der Linden V.
        • et al.
        Follow-up brain imaging of 37 children with congenital Zika syndrome: case series study.
        BMJ. 2017; 359: j4188
        • Adebanjo T.
        • Godfred-Cato S.
        • Viens L.
        • et al.
        Update: interim guidance for the diagnosis, evaluation, and management of infants with possible congenital Zika virus infection—United States, October 2017.
        MMWR Morb Mortal Wkly Rep. 2017; 66: 1089-1099
        • Shapiro-Mendoza C.K.
        • Rice M.E.
        • Galang R.R.
        • et al.
        Pregnancy outcomes after maternal Zika virus infection during pregnancy—US Territories, January 1, 2016–April 25, 2017.
        MMWR Morb Mortal Wkly Rep. 2017; 66: 615-621
        • Hoen B.
        • Schaub B.
        • Funk A.L.
        • et al.
        Pregnancy outcomes after ZIKV infection in French Territories in the Americas.
        N Engl J Med. 2018; 378: 985-994
        • Walker C.L.
        • Merriam A.A.
        • Ohuma E.O.
        • et al.
        Femur-sparing pattern of abnormal fetal growth in pregnant women from New York City after maternal Zika virus infection.
        Am J Obstet Gynecol. 2018; 219: 187.e1-187.e20
        • Hall N.B.
        • Broussard K.
        • Evert N.
        • Canfield M.
        Notes from the field: Zika virus-associated neonatal birth defects surveillance—Texas, January 2016–July 2017.
        MMWR Morb Mortal Wkly Rep. 2017; 66: 835-836
        • Honein M.A.
        • Dawson A.L.
        • Petersen E.E.
        • et al.
        Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy.
        JAMA. 2017; 317: 59-68
        • Adams Waldorf K.M.
        • Olson E.M.
        • Nelson B.R.
        • Little M.E.
        • Rajagopal L.
        The aftermath of Zika: need for long-term monitoring of exposed children.
        Trends Microbiol. 2018; 26: 729-732
        • Brasil P.
        • Pereira Jr., J.P.
        • Moreira M.E.
        • et al.
        Zika virus infection in pregnant women in Rio de Janeiro.
        N Engl J Med. 2016; 375: 2321-2334
        • Chan J.F.
        • Zhang A.J.
        • Chan C.C.
        • et al.
        Zika virus infection in dexamethasone-immunosuppressed mice demonstrating disseminated infection with multi-organ involvement including orchitis effectively treated by recombinant type I interferons.
        EBio Med. 2016; 14: 112-122
        • Miner J.J.
        • Diamond M.S.
        Zika virus pathogenesis and tissue tropism.
        Cell Host Microbe. 2017; 21: 134-142
        • Miner J.J.
        • Cao B.
        • Govero J.
        • et al.
        Zika virus infection during pregnancy in mice causes placental damage and fetal demise.
        Cell. 2016; 165: 1081-1091
        • Adams Waldorf K.M.
        • Stencel-Baerenwald J.E.
        • Kapur R.P.
        • et al.
        Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate.
        Nat Med. 2016; 22: 1256-1259
        • Lazear H.M.
        • Govero J.
        • Smith A.M.
        • et al.
        A mouse model of Zika virus pathogenesis.
        Cell Host Microbe. 2016; 9: 720-730
        • Rossi S.L.
        • Tesh R.B.
        • Azar S.R.
        • et al.
        Characterization of a novel murine model to study Zika virus.
        Am J Trop Med Hyg. 2016; 94: 1362-1369
        • Cavalcanti D.D.
        • Alves L.V.
        • Furtado G.J.
        • et al.
        Echocardiographic findings in infants with presumed congenital Zika syndrome: Retrospective case series study.
        PloS One. 2017; 12: e0175065
        • Orofino D.H.G.
        • Passos S.R.L.
        • de Oliveira R.V.C.
        • et al.
        Cardiac findings in infants with in utero exposure to Zika virus—a cross sectional study.
        PLoS Negl Trop Dis. 2018; 12: e0006362
        • Angelidou A.
        • Michael Z.
        • Hotz A.
        • et al.
        Is there more to Zika? Complex cardiac disease in a case of congenital Zika syndrome.
        Neonatology. 2018; 113: 177-182
        • Matusali G.
        • Houzet L.
        • Satie A.P.
        • et al.
        Zika virus infects human testicular tissue and germ cells.
        J Clin Invest. 2018 Sep 10; (pii: 121735. https://doi.org/10.1172/JCI121735. [Epub ahead of print] PMID: 30063220.)
        • Medina F.A.
        • Torres G.
        • Acevedo J.
        • et al.
        Duration of infectious Zika virus in semen and serum.
        J Infect Dis. 2018 Jul 27; (https://doi.org/10.1093/infdis/jiy462. [Epub ahead of print])
        • Garcia-Bujalance S.
        • Gutierrez-Arroyo A.
        • De la Calle F.
        • et al.
        Persistence and infectivity of Zika virus in semen after returning from endemic areas: report of 5 cases.
        J Clin Virol. 2017; 96: 110-115
        • McDonald E.M.
        • Duggal N.K.
        • Ritter J.M.
        • Brault A.C.
        Infection of epididymal epithelial cells and leukocytes drives seminal shedding of Zika virus in a mouse model.
        PLoS Negl Trop Dis. 2018; 12: e0006691
        • Robinson C.L.
        • Chong A.C.N.
        • Ashbrook A.W.
        • et al.
        Male germ cells support long-term propagation of Zika virus.
        Nat Commun. 2018; 9: 2090
        • Aleman T.S.
        • Ventura C.V.
        • Cavalcanti M.M.
        • et al.
        Quantitative assessment of microstructural changes of the retina in infants with congenital Zika syndrome.
        JAMA Ophthalmol. 2017; 135: 1069-1076
        • Singh P.K.
        • Guest J.M.
        • Kanwar M.
        • et al.
        Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes.
        JCI Insight. 2017; 2: e92340
        • Britt W.J.
        Adverse outcomes of pregnancy-associated Zika virus infection.
        Semin Perinatol. 2018; 42: 155-167
        • Muffat J.
        • Li Y.
        • Omer A.
        • et al.
        Human induced pluripotent stem cell-derived glial cells and neural progenitors display divergent responses to Zika and dengue infections.
        Proc Natl Acad Sci USA. 2018; 115: 7117-7122
        • Szaba F.M.
        • Tighe M.
        • Kummer L.W.
        • et al.
        Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection.
        PLoS Pathogens. 2018; 14: e1006994
        • Nguyen S.M.
        • Antony K.M.
        • Dudley D.M.
        • et al.
        Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.
        PLoS Pathogens. 2017; 13: e1006378
        • Hirsch A.J.
        • Roberts V.H.J.
        • Grigsby P.L.
        • et al.
        Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology.
        Nat Commun. 2018; 9: 263
        • Martines R.B.
        • Bhatnagar J.
        • de Oliveira Ramos A.M.
        • et al.
        Pathology of congenital Zika syndrome in Brazil: a case series.
        Lancet. 2016; 388: 898-904
        • Ritter J.M.
        • Martines R.B.
        • Zaki S.R.
        Zika virus: pathology from the pandemic.
        Arch Pathol Lab Med. 2017; 141: 49-59
        • Mavigner M.
        • Raper J.
        • Kovacs-Balint Z.
        • et al.
        Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques.
        Sci Transl Med. 2018; 10
        • Spalding K.L.
        • Bergmann O.
        • Alkass K.
        • et al.
        Dynamics of hippocampal neurogenesis in adult humans.
        Cell. 2013; 153: 1219-1227
        • Sorrells S.F.
        • Paredes M.F.
        • Cebrian-Silla A.
        • et al.
        Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.
        Nature. 2018; 555: 377-381
        • Boldrini M.
        • Fulmore C.A.
        • Tartt A.N.
        • et al.
        Human hippocampal neurogenesis persists throughout aging.
        Cell Stem Cell. 2018; 22: 589-599.e5
        • Kempermann G.
        • Gage F.H.
        • Aigner L.
        • et al.
        Human adult neurogenesis: evidence and remaining questions.
        Cell Stem Cell. 2018;
        • Goncalves J.T.
        • Schafer S.T.
        • Gage F.H.
        Adult neurogenesis in the hippocampus: from stem cells to behavior.
        Cel. 2016; 167: 897-914
        • Toda T.
        • Parylak S.L.
        • Linker S.B.
        • Gage F.H.
        The role of adult hippocampal neurogenesis in brain health and disease.
        Mol Psychiatry. 2018 Apr 20; (https://doi.org/10.1038/s41380-018-0036-2. [Epub ahead of print])
        • Silva A.A.
        • Barbieri M.A.
        • Alves M.T.
        • et al.
        Prevalence and risk factors for microcephaly at birth in Brazil in 2010.
        Pediatrics. 2018; 141
        • Oliveira Melo A.S.
        • Malinger G.
        • Ximenes R.
        • Szejnfeld P.O.
        • Alves Sampaio S.
        • Bispo de Filippis A.M.
        Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg?.
        Ultrasound Obstet Gynecol. 2016; 47: 6-7
        • Cugola F.R.
        • Fernandes I.R.
        • Russo F.B.
        • et al.
        The Brazilian Zika virus strain causes birth defects in experimental models.
        Nature. 2016; 534: 267-271
        • Uraki R.
        • Jurado K.A.
        • Hwang J.
        • et al.
        Fetal growth restriction caused by sexual transmission of Zika virus in mice.
        J Infect Dis. 2017; 215: 1720-1724
        • van der Eijk A.A.
        • van Genderen P.J.
        • Verdijk R.M.
        • et al.
        Miscarriage associated with Zika virus infection.
        N Engl J Med. 2016; 375: 1002-1004
        • Schaub B.
        • Monthieux A.
        • Najihoullah F.
        • et al.
        Late miscarriage: another Zika concern?.
        Eur J Obstet Gynecol Reprod Biol. 2016; 207: 240-241
        • Magnani D.M.
        • Rogers T.F.
        • Maness N.J.
        • et al.
        Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques.
        Nat Commun. 2018; 9: 1624
        • Seferovic M.
        • Martin C.S.
        • Tardif S.D.
        • et al.
        Experimental Zika virus infection in the pregnant common marmoset induces spontaneous fetal loss and neurodevelopmental abnormalities.
        Sci Rep. 2018; 8: 6851
        • Wilcox A.J.
        • Weinberg C.R.
        • O'Connor J.F.
        • et al.
        Incidence of early loss of pregnancy.
        N Engl J Med. 1988; 319: 189-194
        • Dudley D.M.
        • Van Rompay K.K.
        • Coffey L.L.
        • et al.
        Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates.
        Nat Med. 2018; 24: 1104-1107
        • Yockey L.J.
        • Jurado K.A.
        • Arora N.
        • et al.
        Type I interferons instigate fetal demise after Zika virus infection.
        Sci Immunol. 2018; 3
        • Blencowe H.
        • Cousens S.
        • Jassir F.B.
        • et al.
        National, regional, and worldwide estimates of stillbirth rates in 2015, with trends from 2000: a systematic analysis.
        Lancet Glob Health. 2016; 4: e98-e108
        • Lucchese G.
        • Kanduc D.
        Zika virus and autoimmunity: from microcephaly to Guillain-Barre syndrome, and beyond.
        Autoimmun Rev. 2016; 15: 801-808
        • Barzon L.
        • Pacenti M.
        • Franchin E.
        • et al.
        Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016.
        Euro Surveill. 2016; 21
        • Aid M.
        • Abbink P.
        • Larocca R.A.
        • et al.
        Zika virus persistence in the central nervous system and lymph nodes of rhesus monkeys.
        Cell. 2017; 169: 610-620.e14
        • Gaskell K.M.
        • Houlihan C.
        • Nastouli E.
        • Checkley A.M.
        Persistent Zika virus detection in semen in a traveler returning to the United Kingdom from Brazil, 2016.
        Emerg Infect Dis. 2017; 23: 137-139
        • Schaub B.
        • Monthieux A.
        • Najioullah F.
        • Adenet C.
        • Muller F.
        • Cesaire R.
        Persistent maternal Zika viremia: a marker of fetal infection.
        Ultrasound Obstet Gynecol. 2017; 49: 658-660
        • Gonce A.
        • Martinez M.J.
        • Marban-Castro E.
        • et al.
        Spontaneous abortion associated with Zika virus infection and persistent viremia.
        Emerg Infect Dis. 2018; 24: 933-935
        • Lindenbach B.D.
        • Thiel H.-J.
        • Rice C.M.
        Flaviviridae: the viruses and their replication.
        in: Knipe D.M. Howley P.M. Fields virology. 5th ed. Lippincott-Raven Publishers, Philidelphia2007: 1101-1152
        • Suthar M.S.
        • Diamond M.S.
        • Gale M.
        West Nile virus infection and immunity.
        Nat Rev Microbiol. 2013; 11: 115-128
        • Keller B.C.
        • Fredericksen B.L.
        • Samuel M.A.
        • et al.
        Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence.
        J Virol. 2006; 80: 9424-9434
        • Liu W.J.
        • Wang X.J.
        • Mokhonov V.V.
        • Shi P.Y.
        • Randall R.
        • Khromykh A.A.
        Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins.
        J Virol. 2005; 79: 1934-1942
        • Fredericksen B.L.
        • Gale Jr., M.
        West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling.
        J Virol. 2006; 80: 2913-2923
        • Miorin L.
        • Albornoz A.
        • Baba M.M.
        • D'Agaro P.
        • Marcello A.
        Formation of membrane-defined compartments by tick-borne encephalitis virus contributes to the early delay in interferon signaling.
        Virus Res. 2012; 163: 660-666
        • Daffis S.
        • Szretter K.J.
        • Schriewer J.
        • et al.
        2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members.
        Nature. 2010; 468: 452-456
        • Donald C.L.
        • Brennan B.
        • Cumberworth S.L.
        • et al.
        Full genome sequence and sfRNA interferon antagonist activity of Zika virus from Recife, Brazil.
        PLoS Negl Trop Dis. 2016; 10: e0005048
        • Best S.M.
        The many faces of the flavivirus NS5 protein in antagonism of type I interferon signaling.
        J Virol. 2017; 91
        • Grant A.
        • Ponia S.S.
        • Tripathi S.
        • et al.
        Zika virus targets human STAT2 to inhibit type I interferon signaling.
        Cell Host Microbe. 2016; 19: 882-890
        • Hertzog J.
        • Dias Junior A.G.
        • et al.
        Infection with a Brazilian isolate of Zika virus generates RIG-I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signalling.
        Eur J Immunol. 2018; 48: 1120-1136
        • Kumar A.
        • Hou S.
        • Airo A.M.
        • et al.
        Zika virus inhibits type-I interferon production and downstream signaling.
        EMBO Rep. 2016; 17: 1766-1775
        • Xia H.
        • Luo H.
        • Shan C.
        • et al.
        An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction.
        Nat Commun. 2018; 9: 414
        • Wu Y.
        • Liu Q.
        • Zhou J.
        • et al.
        Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro.
        Cell Discov. 2017; 3: 17006
        • Glasner A.
        • Oiknine-Djian E.
        • Weisblum Y.
        • et al.
        Zika virus escapes NK cell detection by upregulating major histocompatibility complex class I molecules.
        J Virol. 2017; 91
        • Lobigs M.
        • Mullbacher A.
        • Regner M.
        MHC class I up-regulation by flaviviruses: immune interaction with unknown advantage to host or pathogen.
        Immunol Cell Biol. 2003; 81: 217-223
        • Avirutnan P.
        • Mehlhop E.
        • Diamond M.S.
        Complement and its role in protection and pathogenesis of flavivirus infections.
        Vaccine. 2008; 26: I100-I107
        • Muller D.A.
        • Young P.R.
        The flavivirus NS1 protein: molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker.
        Antiviral Res. 2013; 98: 192-208
        • Silasi M.
        • Cardenas I.
        • Kwon J.Y.
        • Racicot K.
        • Aldo P.
        • Mor G.
        Viral infections during pregnancy.
        Am J Reprod Immunol (New York, NY: 1989). 2015; 73: 199-213
        • Singer D.B.
        • Rudolph A.J.
        • Rosenberg H.S.
        • Rawls W.E.
        • Boniuk M.
        Pathology of the congenital rubella syndrome.
        J Pediatr. 1967; 71: 665-675
        • Mathur A.
        • Tandon H.O.
        • Mathur K.R.
        • Sarkari N.B.
        • Singh U.K.
        • Chaturvedi U.C.
        Japanese encephalitis virus infection during pregnancy.
        Indian J Med Res. 1985; 81: 9-12
        • Chaturvedi U.C.
        • Mathur A.
        • Chandra A.
        • Das S.K.
        • Tandon H.O.
        • Singh U.K.
        Transplacental infection with Japanese encephalitis virus.
        J Infect Dis. 1980; 141: 712-715
        • Zhang Y.
        • Li X.
        • Chen H.
        • et al.
        Evidence of possible vertical transmission of Tembusu virus in ducks.
        Vet Microbiol. 2015; 179: 149-154
        • Kim K.
        • Shresta S.
        Neuroteratogenic Viruses and lessons for Zika virus models.
        Trends Microbiol. 2016; 24: 622-636
        • Platt D.J.
        • Smith A.M.
        • Arora N.
        • Diamond M.S.
        • Coyne C.B.
        • Miner J.J.
        Zika virus-related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice.
        Sci Transl Med. 2018; 10
        • O'Leary D.R.
        • Kuhn S.
        • Kniss K.L.
        • et al.
        Birth outcomes following West Nile virus infection of pregnant women in the United States: 2003–2004.
        Pediatrics. 2006; 117: e537-e545
        • Bandeira A.C.
        • Campos G.S.
        • Sardi S.I.
        • Rocha V.F.
        • Rocha G.C.
        Neonatal encephalitis due to Chikungunya vertical transmission: first report in Brazil.
        IDCases. 2016; 5: 57-59
        • Gerardin P.
        • Samperiz S.
        • Ramful D.
        • et al.
        Neurocognitive outcome of children exposed to perinatal mother-to-child Chikungunya virus infection: the CHIMERE cohort study on Reunion Island.
        PLoS Negl Trop Dis. 2014; 8: e2996