Abnormal Development - Zika Virus

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Zika virus world map (CDC 2016)
Zika Virus Pregnancy USA (2015-2016)
Zika Virus Pregnancy USA (2015-2016)[1]

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.[2]

Mosquito lifecycle

Mosquito bites lead to an initial infection of skin cells.[3] The virus may also be transmitted transplacentally or during delivery.[4]

Now good evidence, from Brazil and other South American countries, for association with neural abnormalities (microcephaly, vision development, Guillian Barre Syndrome). This possible association in other developmental systems 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: TORCH Infections | Cytomegalovirus | Hepatitis Virus | HIV | Parvovirus | Polio Virus | Rubella Virus | Chickenpox | Lymphocytic Choriomeningitis Virus | Zika Virus | Vaccination | Environmental

Some Recent Findings

Microlissencephaly MRI-01.jpg

  • Congenital Zika Virus Infection: Beyond Neonatal Microcephaly[5] "Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil....Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain)."
  • Modeling Zika Virus Infection in Pregnancy[6] "Collectively, the findings from the stud- ies in mice support the hypothesis that infection during pregnancy with contemporary ZIKV strains causes placental infection and injury and that ZIKV spreads to the fetal brain and kills neuronal progenitor cells, which probably con- tributes to the microcephaly and other congeni- tal malformations that have been observed in human neonates."
  • Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study[7] "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 Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities[8] "The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week. The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated."
  • Zika virus outbreaks prompt warnings to pregnant women[9] "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[10] "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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  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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Search term: Abnormal Development Zika Virus

Irfan A Rather, Jameel B Lone, Vivek K Bajpai, Yong-Ha Park Zika Virus Infection during Pregnancy and Congenital Abnormalities. Front Microbiol: 2017, 8;581 PubMed 28421065

Juan B Yepez, Felipe A Murati, Michele Pettito, Carlos F Peñaranda, Jazmin de Yepez, Gladys Maestre, J Fernando Arevalo, Johns Hopkins Zika Center Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela. JAMA Ophthalmol: 2017; PubMed 28418539

Antonio José Ledo Alves da Cunha, Maria Clara de Magalhães-Barbosa, Fernanda Lima-Setta, Roberto de Andrade Medronho, Arnaldo Prata-Barbosa Microcephaly Case Fatality Rate Associated with Zika Virus Infection in Brazil: Current Estimates. Pediatr. Infect. Dis. J.: 2017, 36(5);528-530 PubMed 28403061

Esaú Custódio João, Maria Isabel Fragoso da Silveira Gouvea, Maria de Lourdes Benamor Teixeira, Wallace Mendes-Silva, Juliana Silva Esteves, Edwiges Motta Santos, Leandro Augusto Ledesma, Ana Paula Gomes, Maria Letícia Cruz Zika Virus Infection Associated With Congenital Birth Defects in a HIV-infected Pregnant Woman. Pediatr. Infect. Dis. J.: 2017, 36(5);500-501 PubMed 28403053

Bin Cao, Michael S Diamond, Indira U Mysorekar Maternal-Fetal Transmission of Zika Virus: Routes and Signals for Infection. J. Interferon Cytokine Res.: 2017; PubMed 28402153

Search term: Zika Virus

Beuy Joob, Viroj Wiwanitkit Zika Virus Infection. Pediatr Emerg Care: 2017; PubMed 28441244

Federica Verna, Paola Modesto, Maria Cristina Radaelli, Danila Raffaella Francese, Enrico Monaci, Rosanna Desiato, Carla Grattarola, Simone Peletto, Andrea Mosca, Giovanni Savini, Rosa Chianese, Vittorio Demicheli, Marino Prearo, Laura Chiavacci, Alessandra Pautasso, Cristina Casalone Control of Mosquito-Borne Diseases in Northwestern Italy: Preparedness from One Season to the Next. Vector Borne Zoonotic Dis.: 2017; PubMed 28437184

Simin Aysel Florescu, Ani Ioana Cotar, Corneliu Petru Popescu, Cornelia Svetlana Ceianu, Mihaela Zaharia, Geta Vancea, Daniel Codreanu, Daniela Badescu, Emanoil Ceausu First Two Imported Cases of Zika Virus Infections in Romania. Vector Borne Zoonotic Dis.: 2017; PubMed 28437183

Carolina Q Sacramento, Gabrielle R de Melo, Caroline S de Freitas, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Miranda, Natalia Fintelman-Rodrigues, Andressa Marttorelli, André C Ferreira, Giselle Barbosa-Lima, Juliana L Abrantes, Yasmine Rangel Vieira, Mônica M Bastos, Eduardo de Mello Volotão, Estevão Portela Nunes, Diogo A Tschoeke, Luciana Leomil, Erick Correia Loiola, Pablo Trindade, Stevens K Rehen, Fernando A Bozza, Patrícia T Bozza, Nubia Boechat, Fabiano L Thompson, Ana M B de Filippis, Karin Brüning, Thiago Moreno L Souza Corrigendum: The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication. Sci Rep: 2017, 7;46772 PubMed 28436989

Essam Mohammed Janahi, Anupam Dhasmana, Vandana Srivastava, Aditya Narayan Sarangi, Sana Raza, Jamal M Arif, Madan Lal Bramha Bhatt, Mohtashim Lohani, Mohammed Yahya Areeshi, Anand Murari Saxena, Shafiul Haque In silico CD4+, CD8+ T-cell and B-cell immunity associated immunogenic epitope prediction and HLA distribution analysis of Zika virus. EXCLI J: 2017, 16;63-72 PubMed 28435428

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.[11]

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

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), Africa. 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.[12]

Documented Outbreaks

  • 2007 - Micronesia island of Yap (Pacific)
  • 2013 - Micronesia island of Yap (Pacific)
  • May 2015 - Brazil (South America)
  • October 2015 - Republic of Cabo Verde (Africa)
  • November 2015 - Suriname, El Salvador, Mexico, Guatemala, Paraguay, and Bolivarian Republic of Venezuela


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.[13]

Links: Malaria


Skull microcephaly
Skull - 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.

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[10] 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


  1. Regina M Simeone, Carrie K Shapiro-Mendoza, Dana Meaney-Delman, Emily E Petersen, Romeo R Galang, Titilope Oduyebo, Brenda Rivera-Garcia, Miguel Valencia-Prado, Kimberly B Newsome, Janice Pérez-Padilla, Tonya R Williams, Matthew Biggerstaff, Denise J Jamieson, Margaret A Honein, Zika and Pregnancy Working Group, Farah Ahmed, Scott Anesi, Kathryn E Arnold, Danielle Barradas, Devra Barter, Jeanne Bertolli, Andrea M Bingham, Jan Bollock, Trish Bosse, Kristy K Bradley, Diane Brady, Catherine M Brown, Katie Bryan, Victoria Buchanan, Ponce D Bullard, Alice Carrigan, Monica Clouse, Sally Cook, Michael Cooper, Sherri Davidson, Ariana DeBarr, Thomas Dobbs, Tambra Dunams, Jeffrey Eason, Amanda Eckert, Paula Eggers, Sascha R Ellington, Amanda Feldpausch, Carolyn R Fredette, Julie Gabel, Maleeka Glover, Michael Gosciminski, Margarita Gay, Robert Haddock, Sheryl Hand, Jessica Hardy, Marie E Bottomley Hartel, Andrew K Hennenfent, Susan L Hills, Jennifer House, Iro Igbinosa, Lucy Im, Hamik Jeff, Sumaiya Khan, Lon Kightlinger, Jean Y Ko, Samir Koirala, Lauren Korhonen, Vikram Krishnasamy, Katie Kurkjian, Margaret Lampe, Sandra Larson, Ellen H Lee, Leah Lind, Scott Lindquist, Jonah Long, Jennifer Macdonald, Jennifer MacFarquhar, Daniel P Mackie, Miguella Mark-Carew, Brennan Martin, Alma Martinez-Quiñones, Janice Matthews-Greer, Sasha A McGee, Joe McLaughlin, Valerie Mock, Esther Muna, Hanna Oltean, Josephine O'Mallan, H Pamela Pagano, Sarah Y Park, Dallin Peterson, Kara N D Polen, Charsey Cole Porse, Carol Y Rao, Abubakar Ropri, Jessica Rinsky, Sara Robinson, Asher Y Rosinger, Irene Ruberto, Elizabeth Schiffman, Christine Scott-Waldron, Shereen Semple, Tyler Sharp, Kirstin Short, Kimberly Signs, Sally A Slavinski, Taryn Stevens, Joseph Sweatlock, Elizabeth A Talbot, Julius Tonzel, Rita Traxler, Sheri Tubach, Clayton Van Houten, Elizabeth VinHatton, Melissa Viray, Daguise Virginie, Michael D Warren, Catherine Waters, Paul White, Tanya Williams, Ann I Winters, Shelley Wood, Ibrahim Zaganjor Possible Zika Virus Infection Among Pregnant Women - United States and Territories, May 2016. MMWR Morb. Mortal. Wkly. Rep.: 2016, 65(20);514-519 PubMed 27248295
  2. Alyssa T Pyke, Michelle T Daly, Jane N Cameron, Peter R Moore, Carmel T Taylor, Glen R Hewitson, Jan L Humphreys, Richard Gair Imported zika virus infection from the cook islands into australia, 2014. PLoS Curr: 2014, 6; PubMed 24944843
  3. Rodolphe Hamel, Ophélie Dejarnac, Sineewanlaya Wichit, Peeraya Ekchariyawat, Aymeric Neyret, Natthanej Luplertlop, Manuel Perera-Lecoin, Pornapat Surasombatpattana, Loïc Talignani, Frédéric Thomas, Van-Mai Cao-Lormeau, Valérie Choumet, Laurence Briant, Philippe Desprès, Ali Amara, Hans Yssel, Dorothée Missé Biology of Zika Virus Infection in Human Skin Cells. J. Virol.: 2015, 89(17);8880-96 PubMed 26085147
  4. M Besnard, S Lastere, A Teissier, Vm Cao-Lormeau, D Musso Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill.: 2014, 19(13); PubMed 24721538
  5. Adriana Suely de Oliveira Melo, Renato Santana Aguiar, Melania Maria Ramos Amorim, Monica B Arruda, Fabiana de Oliveira Melo, Suelem Taís Clementino Ribeiro, Alba Gean Medeiros Batista, Thales Ferreira, Mayra Pereira Dos Santos, Virgínia Vilar Sampaio, Sarah Rogéria Martins Moura, Luciana Portela Rabello, Clarissa Emanuelle Gonzaga, Gustavo Malinger, Renato Ximenes, Patricia Soares de Oliveira-Szejnfeld, Fernanda Tovar-Moll, Leila Chimelli, Paola Paz Silveira, Rodrigo Delvechio, Luiza Higa, Loraine Campanati, Rita M R Nogueira, Ana Maria Bispo Filippis, Jacob Szejnfeld, Carolina Moreira Voloch, Orlando C Ferreira, Rodrigo M Brindeiro, Amilcar Tanuri Congenital Zika Virus Infection: Beyond Neonatal Microcephaly. JAMA Neurol: 2016; PubMed 27695855
  6. Indira U Mysorekar, Michael S Diamond Modeling Zika Virus Infection in Pregnancy. N. Engl. J. Med.: 2016; PubMed 27433842
  7. Maria de Fatima Vasco Aragao, Vanessa van der Linden, Alessandra Mertens Brainer-Lima, Regina Ramos Coeli, Maria Angela Rocha, Paula Sobral da Silva, Maria Durce Costa Gomes de Carvalho, Ana van der Linden, Arthur Cesario de Holanda, Marcelo Moraes Valenca 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 PubMed 27075009 | BMJ.
  8. Rita W Driggers, Cheng-Ying Ho, Essi M Korhonen, Suvi Kuivanen, Anne J Jääskeläinen, Teemu Smura, Avi Rosenberg, D Ashley Hill, Roberta L DeBiasi, Gilbert Vezina, Julia Timofeev, Fausto J Rodriguez, Lev Levanov, Jennifer Razak, Preetha Iyengar, Andrew Hennenfent, Richard Kennedy, Robert Lanciotti, Adre du Plessis, Olli Vapalahti Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities. N. Engl. J. Med.: 2016; PubMed 27028667
  9. Ingrid Torjesen Zika virus outbreaks prompt warnings to pregnant women. BMJ: 2016, 352;i500 PubMed 26813766
  10. 10.0 10.1 Bruno de Paula Freitas, João Rafael de Oliveira Dias, Juliana Prazeres, Gielson Almeida Sacramento, Albert Icksang Ko, Maurício Maia, Rubens Belfort Ocular Findings in Infants With Microcephaly Associated With Presumed Zika Virus Congenital Infection in Salvador, Brazil. JAMA Ophthalmol: 2016; PubMed 26865554
  11. Goro Kuno, Gwong-Jen J Chang Biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends. Clin. Microbiol. Rev.: 2005, 18(4);608-37 PubMed 16223950
  12. Alyssa T Pyke, Michelle T Daly, Jane N Cameron, Peter R Moore, Carmel T Taylor, Glen R Hewitson, Jan L Humphreys, Richard Gair Imported zika virus infection from the cook islands into australia, 2014. PLoS Curr: 2014, 6; PubMed 24944843
  13. Shin-ya Ohba, Kazunori Ohashi, Endang Pujiyati, Yukiko Higa, Hitoshi Kawada, Nobuaki Mito, Masahiro Takagi The effect of pyriproxyfen as a "population growth regulator" against Aedes albopictus under semi-field conditions. PLoS ONE: 2013, 8(7);e67045 PubMed 23843982



Giuseppe Marano, Simonetta Pupella, Stefania Vaglio, Giancarlo M Liumbruno, Giuliano Grazzini Zika virus and the never-ending story of emerging pathogens and transfusion medicine. Blood Transfus: 2015;1-6 PubMed 26674815


Carlos Brisola Marcondes, Maria de Fátima Freire de Melo Ximenes Zika virus in Brazil and the danger of infestation by Aedes (Stegomyia) mosquitoes. Rev. Soc. Bras. Med. Trop.: 2015; PubMed 26689277

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Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Zika Virus. Retrieved April 26, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Zika_Virus

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