Abnormal Development - Zika Virus

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Introduction

Zika virus world map (CDC 2016)

Zika virus (ZIKV) is a mosquito-borne flavivirus related to dengue virus first isolated from a rhesus monkey in Zika forest, Uganda (1947). Transmitted by mosquitoes (Aedes aegypti) it was then identified in humans in Nigeria in 1954 and subsequently in South America, Asia and Pacific regions. More recently in Australia from returning travellers.[1]

Mosquito lifecycle

Mosquito bites lead to an initial infection of skin cells.[2] The virus may also be transmitted transplacentally or during delivery.[3]

Some limited evidence, from Brazil, for association with neural abnormalities (microcephaly, vision development, Guillian Barre Syndrome). This possible association requires more clinical and scientific evidence before being confirmed.


"Although a causal link between Zika infection in pregnancy and microcephaly - and I must emphasise - has not been established, the circumstantial evidence is suggestive and extremely worrisome" (Margaret Chan, WHO General Director).



Viral Links: viral infection | TORCH | cytomegalovirus | hepatitis | HIV | parvovirus | polio | rubella virus | chickenpox | Lymphocytic Choriomeningitis Virus | Zika virus | human papillomavirus | rotavirus | West Nile virus | varicella virus | vaccination | zoonotic infection | environment
Historic Embryology - Viral 
1941 Rubella Cataracts | 1944 Rubella Defects

Some Recent Findings

Microlissencephaly MRI-01.jpg

  • Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study[4] "23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus-the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. ...Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem."
  • Zika virus outbreaks prompt warnings to pregnant women[5] "The rapid spread of Zika virus in the Americas, where there is little population immunity, is a major concern, especially given the possible link between infection during pregnancy and the congenital abnormality microcephaly, the World Health Organization has warned. Margaret Chan, WHO’s director general, said, “Although a causal link between Zika infection in pregnancy and microcephaly has not been established, the circumstantial evidence is suggestive and extremely worrisome. An increased occurrence of neurological syndromes, noted in some countries coincident with arrival of the virus, adds to the concern."
  • Ocular Findings in Infants With Microcephaly Associated With Presumed Zika Virus Congenital Infection in Salvador, Brazil[6] "Twenty-three of 29 mothers (79.3%) reported suspected ZIKV infection signs and symptoms during pregnancy, 18 in the first trimester, 4 in the second trimester, and 1 in the third trimester. Of the 29 infants (58 eyes) examined (18 [62.1%] female), ocular abnormalities were present in 17 eyes (29.3%) of 10 children (34.5%). Bilateral findings were found in 7 of 10 patients presenting with ocular lesions, the most common of which were focal pigment mottling of the retina and chorioretinal atrophy in 11 of the 17 eyes with abnormalities (64.7%), followed by optic nerve abnormalities in 8 eyes (47.1%), bilateral iris coloboma in 1 patient (2 eyes [11.8%]), and lens subluxation in 1 eye (5.9%)."
More recent papers
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Search term: Abnormal Development Zika Virus

<pubmed limit=5>Abnormal Development Zika Virus</pubmed>

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<pubmed limit=5>Zika Virus</pubmed>

Virus Structure

Virus particles are 40 nm in diameter, with an outer envelope, and an inner dense core. ZIKV is an RNA virus containing 10,794 nucleotides encoding 3,419 amino acids.[7]

Zika virus Zika virions (red circles)
Zika virus TEM01.jpg Zika virus TEM02.jpg

Lineage: Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; Flavivirus; Spondweni virus group

Zika virus conserved domains.jpg

Virus Translation - 3,419 amino acids
MKNPKEEIRRIRIVNMLKRGVARVNPLGGLKRLPAGLLLGHGPIRMVLAILAFLRFTAIKPSLGLINRWGSVGKKEAMEIIKKFKKDLAAMLRIINARKERKRRGADTSIGIIGLLLTTAMAAEITRRGSAYYMYLDRSDAGKAISFATTLGVNKCHVQIMDLGHMCDATMSYECPMLDEGVEPDDVDCWCNTTSTWVVYGTCHHKKGEARRSRRAVTLPSHSTRKLQTRSQTWLESREYTKHLIKVENWIFRNPGFALVAVAIAWLLGSSTSQKVIYLVMILLIAPAYSIRCIGVSNRDFVEGMSGGTWVDVVLEHGGCVTVMAQDKPTVDIELVTTTVSNMAEVRSYCYEASISDMASDSRCPTQGEAYLDKQSDTQYVCKRTLVDRGWGNGCGLFGKGSLVTCAKFTCSKKMTGKSIQPENLEYRIMLSVHGSQHSGMIGYETDEDRAKVEVTPNSPRAEATLGGFGSLGLDCEPRTGLDFSDLYYLTMNNKHWLVHKEWFHDIPLPWHAGADTGTPHWNNKEALVEFKDAHAKRQTVVVLGSQEGAVHTALAGALEAEMDGAKGRLFSGHLKCRLKMDKLRLKGVSYSLCTAAFTFTKVPAETLHGTVTVEVQYAGTDGPCKIPVQMAVDMQTLTPVGRLITANPVITESTENSKMMLELDPPFGDSYIVIGVGDKKITHHWHRSGSTIGKAFEATVRGAKRMAVLGDTAWDFGSVGGVFNSLGKGIHQIFGAAFKSLFGGMSWFSQILIGTLLVWLGLNTKNGSISLTCLALGGVMIFLSTAVSADVGCSVDFSKKETRCGTGVFIYNDVEAWRDRYKYHPDSPRRLAAAVKQAWEEGICGISSVSRMENIMWKSVEGELNAILEENGVQLTVVVGSVKNPMWRGPQRLPVPVNELPHGWKAWGKSYFVRAAKTNNSFVVDGDTLKECPLEHRAWNSFLVEDHGFGVFHTSVWLKVREDYSLECDPAVIGTAVKGREAAHSDLGYWIESEKNDTWRLKRAHLIEMKTCEWPKSHTLWTDGVEESDLIIPKSLAGPLSHHNTREGYRTQVKGPWHSEELEIRFEECPGTKVYVEETCGTRGPSLRSTTASGRVIEEWCCRECTMPPLSFRAKDGCWYGMEIRPRKEPESNLVRSMVTAGSTDHMDHFSLGVLVILLMVQEGLKKRMTTKIIMSTSMAVLVVMILGGFSMSDLAKLVILMGATFAEMNTGGDVAHLALVAAFKVRPALLVSFIFRANWTPRESMLLALASCLLQTAISALEGDLMVLINGFALAWLAIRAMAVPRTDNIALPILAALTPLARGTLLVAWRAGLATCGGIMLLSLKGKGSVKKNLPFVMALGLTAVRVVDPINVVGLLLLTRSGKRSWPPSEVLTAVGLICALAGGFAKADIEMAGPMAAVGLLIVSYVVSGKSVDMYIERAGDITWEKDAEVTGNSPRLDVALDESGDFSLVEEDGPPMREIILKVVLMAICGMNPIAIPFAAGAWYVYVKTGKRSGALWDVPAPKEVKKGETTDGVYRVMTRRLLGSTQVGVGVMQEGVFHTMWHVTKGAALRSGEGRLDPYWGDVKQDLVSYCGPWKLDAAWDGLSEVQLLAVPPGERARNIQTLPGIFKTKDGDIGAVALDYPAGTSGSPILDKCGRVIGLYGNGVVIKNGSYVSAITQGKREEETPVECFEPSMLKKKQLTVLDLHPGAGKTRRVLPEIVREAIKKRLRTVILAPTRVVAAEMEEALRGLPVRYMTTAVNVTHSGTEIVDLMCHATFTSRLLQPIRVPNYNLNIMDEAHFTDPSSIAARGYISTRVEMGEAAAIFMTATPPGTRDAFPDSNSPIMDTEVEVPERAWSSGFDWVTDHSGKTVWFVPSVRNGNEIAACLTKAGKRVIQLSRKTFETEFQKTKNQEWDFVITTDISEMGANFKADRVIDSRRCLKPVILDGERVILAGPMPVTHASAAQRRGRIGRNPNKPGDEYMYGGGCAETDEGHAHWLEARMLLDNIYLQDGLIASLYRPEADKVAAIEGEFKLRTEQRKTFVELMKRGDLPVWLAYQVASAGITYTDRRWCFDGTTNNTIMEDSVPAEVWTKYGEKRVLKPRWMDARVCSDHAALKSFKEFAAGKRGAALGVMEALGTLPGHMTERFQEAIDNLAVLMRAETGSRPYKAAAAQLPETLETIMLLGLLGTVSLGIFFVLMRNKGIGKMGFGMVTLGASAWLMWLSEIEPARIACVLIVVFLLLVVLIPEPEKQRSPQDNQMAIIIMVAVGLLGLITANELGWLERTKNDIAHLMGRREEGATMGFSMDIDLRPASAWAIYAALTTLITPAVQHAVTTSYNNYSLMAMATQAGVLFGMGKGMPFMHGDLGVPLLMMGCYSQLTPLTLIVAIILLVAHYMYLIPGLQAAAARAAQKRTAAGIMKNPVVDGIVVTDIDTMTIDPQVEKKMGQVLLIAVAISSAVLLRTAWGWGEAGALITAATSTLWEGSPNKYWNSSTATSLCNIFRGSYLAGASLIYTVTRNAGLVKRRGGGTGETLGEKWKARLNQMSALEFYSYKKSGITEVCREEARRALKDGVATGGHAVSRGSAKIRWLEERGYLQPYGKVVDLGCGRGGWSYYAATIRKVQEVRGYTKGGPGHEEPMLVQSYGWNIVRLKSGVDVFHMAAEPCDTLLCDIGESSSSPEVEETRTLRVLSMVGDWLEKRPGAFCIKVLCPYTSTMMETMERLQRRHGGGLVRVPLCRNSTHEMYWVSGAKSNIIKSVSTTSQLLLGRMDGPRRPVKYEEDVNLGSGTRAVASCAEAPNMKIIGRRIERIRNEHAETWFLDENHPYRTWAYHGSYEAPTQGSASSLVNGVVRLLSKPWDVVTGVTGIAMTDTTPYGQQRVFKEKVDTRVPDPQEGTRQVMNIVSSWLWKELGKRKRPRVCTKEEFINKVRSNAALGAIFEEEKEWKTAVEAVNDPRFWALVDREREHHLRGECHSCVYNMMGKREKKQGEFGKAKGSRAIWYMWLGARFLEFEALGFLNEDHWMGRENSGGGVEGLGLQRLGYILEEMNRAPGGKMYADDTAGWDTRISKFDLENEALITNQMEEGHRTLALAVIKYTYQNKVVKVLRPAEGGKTVMDIISRQDQRGSGQVVTYALNTFTNLVVQLIRNMEAEEVLEMQDLWLLRKPEKVTRWLQSNGWDRLKRMAVSGDDCVVKPIDDRFAHALRFLNDMGKVRKDTQEWKPSTGWSNWEEVPFCSHHFNKLYLKDGRSIVVPCRHQDELIGRARVSPGAGWSIRETACLAKSYAQMWQLLYFHRRDLRLMANAICSAVPVDWVPTGRTTWSIHGKGEWMTTEDMLMVWNRVWIEENDHMEDKTPVTKWTDIPYLGKREDLWCGSLIGHRPRTTWAENIKDTVNMVRRIIGDEEKYMDYLSTQVRYLGEEGSTPGVL

Zika History

Zika virus (ZIKV) is a mosquito-borne flavivirus related to dengue virus first isolated from a rhesus monkey in Zika forest, Uganda (1947). Transmitted by mosquitoes (Aedes aegypti) it was then identified in humans in Nigeria in 1954 and subsequently in South America, Asia and Pacific regions. More recently in Australia from returning travellers.[8]


Pyriproxyfen

Pyriproxyfen structure
Pyriproxyfen structure

(C20H19NO3) A chemical larvicide used to control mosquito populations, and therefore mosquito-bourns infections. A juvenile hormone analog to insect growth regulator (IGR), inhibiting metamorphosis and embryogenesis in several insects. Suggested that the chemical exposure can act at two levels; firstly the blood-fed females may carry the chemical to the larval habitats, thereby inhibiting adult emergence;secondly that tarsal contact with the chemical may inhibit egg maturation in adult mosquitoes.[9]


Links: Malaria

Microcephaly

Microcephaly describes an abnormality of development resulting in a small skull cranium marked by premature fusion of the skull sutures and also under-developed brain. Further scientific study/evidence is required to show a direct link with the virus.

International Classification of Diseases XVII Congenital Malformations

Congenital malformations of the nervous system (Q00-Q07)

  • Q02 Microcephaly Incl.: Hydromicrocephaly Micrencephalon Excl.: Meckel-Gruber syndrome (Q61.9)


Links: Skull Development | Neural System - Abnormalities | International Classification of Diseases XVII Congenital Malformations

Vision Abnormalities

Some viral infections (herpes and rubella) are known to cause developmental vision abnormalities. A clinical study[6] of infants from Zika infected mothers in Brazil have described vision abnormalities including:

  • bilateral ocular lesions
  • focal pigment mottling of the retina
  • chorioretinal atrophy
  • optic nerve abnormalities
iris coloboma
  • lens subluxation
Links: Vision Abnormalities

References

  1. <pubmed>24944843</pubmed>
  2. <pubmed>26085147</pubmed>
  3. <pubmed>24721538</pubmed>
  4. <pubmed>27075009</pubmed>| BMJ.
  5. <pubmed>26813766</pubmed>
  6. 6.0 6.1 <pubmed>26865554</pubmed>
  7. <pubmed>16223950</pubmed>
  8. <pubmed>24944843</pubmed>
  9. <pubmed>23843982</pubmed>

Textbooks


Reviews

<pubmed>26674815</pubmed>

Articles

<pubmed>26689277</pubmed>


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Cite this page: Hill, M.A. (2024, March 28) Embryology Abnormal Development - Zika Virus. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Zika_Virus

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G