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Abstract

An infectious agent’s pathogenic and transmission potential is heavily influenced by early events during the asymptomatic or subclinical phase of disease. During this phase, the presence of infectious agent may be relatively low. An important example of this is Zika virus (ZIKV), which can cross the placenta and infect the foetus, even in mothers with subclinical infections. These subclinical infections represent roughly 80 % of all human infections. Initial ZIKV pathogenesis studies were performed in type I interferon receptor (IFNAR) knockout mice. Blunting the interferon response resulted in robust infectivity, and increased the utility of mice to model ZIKV infections. However, due to the removal of the interferon response, the use of these models impedes full characterization of immune responses to ZIKV-related pathologies. Moreover, IFNAR-deficient models represent severe disease whereas less is known regarding subclinical infections. Investigation of the anti-viral immune response elicited at the maternal-foetal interface is critical to fully understand mechanisms involved in foetal infection, foetal development, and disease processes recognized to occur during subclinical maternal infections. Thus, immunocompetent experimental models that recapitulate natural infections are needed. We have established subclinical intravaginal ZIKV infections in mice and guinea pigs. We found that these infections resulted in: the presence of both ZIKV RNA transcripts and infectious virus in maternal and placental tissues, establishment of foetal infections and ZIKV-mediated CXCL10 expression. These models will aid in discerning the mechanisms of subclinical ZIKV mother-to-offspring transmission, and by extension can be used to investigate other maternal infections that impact foetal development.

Funding
This study was supported by the:
  • College of Veterinary Medicine and Biomedical Sciences, Colorado State University (Award CRC)
    • Principle Award Recipient: CandaceK. Mathiason
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2021-08-19
2024-07-24
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References

  1. Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M et al. Zika virus associated with microcephaly. N Engl J Med 2016; 374:951–958 [View Article]
    [Google Scholar]
  2. Paixao ES, Leong WY, Rodrigues LC, Wilder-Smith A. Asymptomatic prenatal Zika virus infection and congenital Zika syndrome. In Open forum infectious diseases Vol Vol. 5, no.4 US: Oxford University Press; 2018 p ofy073
    [Google Scholar]
  3. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL et al. Zika virus outbreak on Yap Island, federated states of Micronesia. N Engl J Med 2009; 360:2536–2543 [View Article]
    [Google Scholar]
  4. Ticconi C, Rezza G. Defining Zika virus infection in pregnant women. Pathog Glob Health 2019; 113:290 [View Article] [PubMed]
    [Google Scholar]
  5. Adachi K, Nielsen-Saines K. Zika clinical updates: implications for pediatrics. Curr Opin Pediatr 2018; 30:105 [View Article] [PubMed]
    [Google Scholar]
  6. Pan American Health Organization Epidemiological update: dengue and other arboviruses - 10 june 2020; 2020 https://www.paho.org/en/documents/epidemiological-update-dengue-and-other-arboviruses-10-june-2020
  7. Booth M. Climate change and the neglected tropical diseases. In Advances in parasitology Vol 100 Academic Press; 2018 pp 39–126
    [Google Scholar]
  8. Bradley MP, Nagamine CM. Animal models of Zika virus. Comp Med 2017; 67:242–252 [PubMed]
    [Google Scholar]
  9. Kumar M, Krause KK, Azouz F, Nakano E, Nerurkar VR. A guinea pig model of Zika virus infection. Virol J 2017; 14:75 [View Article] [PubMed]
    [Google Scholar]
  10. Bierle CJ, Fernández-Alarcón C, Hernandez-Alvarado N, Zabeli JC, Janus BC et al. Assessing Zika virus replication and the development of Zika-specific antibodies after a mid-gestation viral challenge in guinea pigs. PLoS One 2017; 12:e0187720 [View Article] [PubMed]
    [Google Scholar]
  11. Deng YQ, Zhang NN, Li XF, Wang YQ, Tian M et al. Intranasal infection and contact transmission of Zika virus in guinea pigs. Nat Commun 2017; 8:1–8
    [Google Scholar]
  12. Miller LJ, Nasar F, Schellhase CW, Norris SL, Kimmel AE et al. Zika virus infection in Syrian golden hamsters and strain 13 guinea pigs. Am J Trop Med Hyg 2018; 98:864–867 [View Article] [PubMed]
    [Google Scholar]
  13. Weger-Lucarelli J, Duggal NK, Bullard-Feibelman K, Veselinovic M, Romo H et al. Development and characterization of recombinant virus generated from a New World Zika virus infectious clone. J Virol 2017; 91:
    [Google Scholar]
  14. Grant A, Ponia SS, Tripathi S, Balasubramaniam V, Miorin L et al. Zika virus targets human STAT2 to inhibit type I interferon signaling. Cell Host & Microbe 2016; 19:882–890 [View Article]
    [Google Scholar]
  15. Bueno MG, Martinez N, Abdalla L, Duarte dos Santos CN, Chame M. Animals in the Zika virus life cycle: what to expect from megadiverse Latin American countries. PLoS Negl Trop Dis 2016; 10:e0005073 [View Article] [PubMed]
    [Google Scholar]
  16. Gutiérrez-Bugallo G, Piedra LA, Rodriguez M, Bisset JA, Lourenço-de-Oliveira R et al. Vector-borne transmission and evolution of Zika virus. Nat Ecol Evol 2019; 3:561–569 [View Article]
    [Google Scholar]
  17. Musso D, Rouault E, Teissier A, Lanteri MC, Zisou K et al. Molecular detection of Zika virus in blood and RNA load determination during the French Polynesian outbreak. J Med Virol 2017; 89:1505–1510 [View Article] [PubMed]
    [Google Scholar]
  18. Theel ES, Hata DJ. Diagnostic testing for Zika virus: a postoutbreak update. Journal of Clinical Microbiology 2018; 56:
    [Google Scholar]
  19. Padilla-Carlin DJ, McMurray DN, Hickey AJ. The guinea pig as a model of infectious diseases. Comp Med 2008; 58:324–340 [PubMed]
    [Google Scholar]
  20. Mess A. The guinea pig placenta: model of placental growth dynamics. Placenta 2007; 28:812–815 [View Article] [PubMed]
    [Google Scholar]
  21. Foy BD, Kobylinski KC, Foy JLC, Blitvich BJ, da Rosa AT et al. Probable non–vector-borne transmission of Zika virus, Colorado, USA. Emerging Infect Dis 2011; 17:880
    [Google Scholar]
  22. Scott JM, Lebratti TJ, Richner JM, Jiang X, Fernandez E et al. Cellular and humoral immunity protect against vaginal Zika virus infection in mice. J Virol 2018; 92: [View Article] [PubMed]
    [Google Scholar]
  23. Khaiboullina SF, Lopes P, de Carvalho TG, Real ALC, Souza DG et al. Host immune response to ZIKV in an immunocompetent embryonic mouse model of intravaginal infection. Viruses 2019; 11:558 [View Article]
    [Google Scholar]
  24. Tang WW, Young MP, Mamidi A, Regla-Nava JA, Kim K et al. A mouse model of Zika virus sexual transmission and vaginal viral replication. Cell Rep 2016; 17:3091–3098 [View Article] [PubMed]
    [Google Scholar]
  25. Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL et al. Vaginal exposure to Zika virus during pregnancy leads to fetal brain infection. Cell 2016; 166:1247–1256 [View Article] [PubMed]
    [Google Scholar]
  26. Giakoumelou S, Wheelhouse N, Cuschieri K, Entrican G, Howie SE et al. The role of infection in miscarriage. Hum Reprod Update 2016; 22:116–133 [View Article] [PubMed]
    [Google Scholar]
  27. Szaba FM et al. Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection. PLoS Pathog 2018; 14:e1006994
    [Google Scholar]
  28. Harman MT, Dobrovolny MP. The development of the external form of the guinea‐pig (Cavia cobaya) between the ages of 21 days and 35 days of gestation. J Morphol 1933; 54:493–519 [View Article]
    [Google Scholar]
  29. Cao B, Diamond MS, Mysorekar IU. Maternal-fetal transmission of Zika virus: Routes and signals for infection. J Interferon Cytokine Res 2017; 37:287–294 [View Article]
    [Google Scholar]
  30. Naveca FG, Pontes GS, Chang AYH, Silva GAVD, Nascimento VAD et al. Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage. Mem Inst Oswaldo Cruz 2018; 113:e170542 [View Article] [PubMed]
    [Google Scholar]
  31. Khaiboullina SF, Uppal T, Sarkar R, Gorzalski A, St Jeor S et al. ZIKV infection regulates inflammasomes pathway for replication in monocytes. Scientific Reports 2017; 7:1–14 [View Article]
    [Google Scholar]
  32. Simonin Y, Erkilic N, Damodar K, Clé M, Desmetz C et al. Zika virus induces strong inflammatory responses and impairs homeostasis and function of the human retinal pigment epithelium. EBioMedicine 2019; 39:315–331 [View Article] [PubMed]
    [Google Scholar]
  33. Lima MC, Mendonça L, Rezende AM, Carrera RM, Anibal-Silva CE et al. The transcriptional and protein profile from human infected neuroprogenitor cells is strongly correlated to Zika virus microcephaly cytokines phenotype evidencing a persistent inflammation in the CNS. Front Immunol 2019; 10:1928
    [Google Scholar]
  34. Kapogiannis BG, Chakhtoura N, Hazra R, Spong CY. Bridging knowledge gaps to understand how Zika virus exposure and infection affect child development. JAMA Pediatr 2017; 171:478–485 [View Article] [PubMed]
    [Google Scholar]
  35. Cooper HJ, Iwamoto M, Lash M, Conners EE, Paladini M et al. Maternal Zika virus infection: Association with small-for-gestational-age neonates and preterm birth. Obstet Gynecol 2019; 134:1197–1204 [View Article]
    [Google Scholar]
  36. Khaiboullina S, Ribeiro FM, Uppal T, Martynova E, Rizvanov A et al. Zika virus transmission through blood tissue barriers. Front Microbiol 2019; 10:1465 [View Article] [PubMed]
    [Google Scholar]
  37. Noronha LD, Zanluca C, Burger M, Suzukawa AA, Azevedo M et al. Zika virus infection at different pregnancy stages: anatomopathological findings, target cells and viral persistence in placental tissues. Front Microbiol 2018; 9:2266 [View Article] [PubMed]
    [Google Scholar]
  38. Hastings AK, Yockey LJ, Jagger BW, Hwang J, Uraki R et al. TAM receptors are not required for Zika virus infection in mice. Cell Rep 2017; 19:558–568 [View Article] [PubMed]
    [Google Scholar]
  39. Duggal NK, McDonald EM, Ritter JM, Brault AC. Sexual transmission of Zika virus enhances in utero transmission in a mouse model. Sci Rep 2018; 8:1–8
    [Google Scholar]
  40. Musso D, Gubler DJ. Zika virus. Clin Microbiol Rev 2016; 29:487–524 [View Article] [PubMed]
    [Google Scholar]
  41. Aagaard KM. Primary human placental trophoblasts are permissive for zika virus (ZIKV) replication. Sci Rep 2017; 7:1–14 [View Article]
    [Google Scholar]
  42. Simoni MK, Jurado KA, Abrahams VM, Fikrig E, Guller S. Zika virus infection of Hofbauer cells. Am J Reprod Immunol 2017; 77:e12613 [View Article]
    [Google Scholar]
  43. Hirsch AJ, Roberts VH, Grigsby PL, Haese N, Schabel MC et al. Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. Nat Commun 2018; 9:1–15 [View Article]
    [Google Scholar]
  44. Reagan-Steiner S, Simeone R, Simon E, Bhatnagar J, Oduyebo T et al. Evaluation of placental and fetal tissue specimens for zika virus infection—50 states and District of Columbia, January–December, 2016. MMWR Morb Mortal Wkly Rep 2017; 66:636–643 [View Article] [PubMed]
    [Google Scholar]
  45. Lazear HM. A mouse model of Zika virus pathogenesis. Cell Host & Microbe 2016; 19:720–730 [View Article]
    [Google Scholar]
  46. Rossi SL. Characterization of a novel murine model to study Zika virus. Am J Trop Med Hyg 2016; 94:1362–1369 [View Article] [PubMed]
    [Google Scholar]
  47. Larocca RA. Vaccine protection against Zika virus from Brazil. Nature 2016; 536:474–478 [View Article] [PubMed]
    [Google Scholar]
  48. Govero J. Zika virus infection damages the testes in mice. Nature 2016; 540:438–442 [View Article] [PubMed]
    [Google Scholar]
  49. Yockey LJ. Type I interferons instigate fetal demise after Zika virus infection. Sci Immunol 2018; 3:19 [View Article]
    [Google Scholar]
  50. Miner JJ. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell 2016; 165:1081–1091 [View Article] [PubMed]
    [Google Scholar]
  51. Cugola FR. The brazilian Zika virus strain causes birth defects in experimental models. Nature5347606 2016267–271
    [Google Scholar]
  52. Wu K-Y. Vertical transmission of Zika virus targeting the radial glial cells affects cortex development of offspring mice. Cell Res 2016; 26:645–654 [View Article] [PubMed]
    [Google Scholar]
  53. Shao Q. Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage. Development 2016; 143:4127–4136 [View Article] [PubMed]
    [Google Scholar]
  54. Noguchi KK. Zika virus infection in the developing mouse produces dramatically different neuropathology dependent on viral strain. J Neurosci 2020; 40:1145–1161 [View Article]
    [Google Scholar]
  55. Saver AE, Crawford SA, Joyce JD, Bertke AS. Route of infection influences Zika virus shedding in a guinea pig model. Cells 2019; 8:1437 [View Article]
    [Google Scholar]
  56. Arora N, Sadovsky Y, Dermody TS, Coyne CB. Microbial vertical transmission during human pregnancy. Cell Host Microbe 2017; 21:561–567 [View Article]
    [Google Scholar]
  57. Gleason CA, Juul SE. Avery’s Diseases of the Newborn E-Book Elsevier Health Sciences; 2017
    [Google Scholar]
  58. Honein MA, Dawson AL, Petersen EE, Jones AM, Lee EH 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 [View Article] [PubMed]
    [Google Scholar]
  59. Du MR, Wang SC, Li DJ. The integrative roles of chemokines at the maternal-fetal interface in early pregnancy. Cell Mol Immunol 2014; 11:438–448 [View Article]
    [Google Scholar]
  60. Sui Y, Potula R, Dhillon N, Pinson D, Li S et al. Neuronal apoptosis is mediated by CXCL10 overexpression in simian human immunodeficiency virus encephalitis. Am J Pathol 2004; 164:1557–1566 [View Article] [PubMed]
    [Google Scholar]
  61. Gotsch F, Romero R, Friel L, Kusanovic JP, Espinoza J et al. CXCL10/IP-10: a missing link between inflammation and anti-angiogenesis in preeclampsia. J Matern Fetal Neonatal Med 2007; 20:777–792 [View Article]
    [Google Scholar]
  62. Liu M, Guo S, Hibbert JM, Jain V, Singh N. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine & growth factor reviews 2011; 22:121–130
    [Google Scholar]
  63. Gorman MJ, Caine EA, Zaitsev K, Begley MC, Weger-Lucarelli J. An immunocompetent mouse model of Zika virus infection. Cell Host & Microbe 2018; 23:672–685 [View Article]
    [Google Scholar]
  64. Foo SS, Chen W, Chan Y, Lee WS, Lee SA. Biomarkers and immunoprofiles associated with fetal abnormalities of ZIKV-positive pregnancies. JCI insight 2018; 3:21
    [Google Scholar]
  65. Jaeger AS. Spondweni virus causes fetal harm in Ifnar1−/− mice and is transmitted by Aedes aegypti mosquitoes. Virology 2020; 547:35–46 [View Article] [PubMed]
    [Google Scholar]
  66. Platt DJ. Zika virus–related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice. Sci Transl Med 2018; 10:426
    [Google Scholar]
  67. O’Leary DR. Birth outcomes following West Nile virus infection of pregnant women in the United States: 2003-2004. Pediatrics 2006; 117:e545–e537
    [Google Scholar]
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