1932

Abstract

Why certain viruses cross the physical barrier of the human placenta but others do not is incompletely understood. Over the past 20 years, we have gained deeper knowledge of intrauterine infection and routes of viral transmission. This review focuses on human viruses that replicate in the placenta, infect the fetus, and cause birth defects, including rubella virus, varicella-zoster virus, parvovirus B19, human cytomegalovirus (CMV), Zika virus (ZIKV), and hepatitis E virus type 1. Detailed discussions include () the architecture of the uterine-placental interface, () studies of placental explants ex vivo that provide insights into the infection and spread of CMV and ZIKV to the fetal compartment and how these viruses undermine early development, and () novel treatments and vaccines that limit viral replication and have the potential to reduce dissemination, vertical transmission and the occurrence of congenital disease.

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2018-09-29
2024-12-10
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Literature Cited

  1. 1.  Gregg NM 1941. Congenital cataract following German measles in the mother. Trans. Ophthamol. Soc. Aust. 3:35–46
    [Google Scholar]
  2. 2.  Benirschke K, Kaufmann P 2000. Pathology of the Human Placenta New York: Springer
    [Google Scholar]
  3. 3.  Silasi M, Cardenas I, Kwon JY, Racicot K, Aldo P, Mor G 2015. Viral infections during pregnancy. Am. J. Reprod. Immunol. 73:199–213
    [Google Scholar]
  4. 4.  Goldenberg RL, McClure EM, Saleem S, Reddy UM 2010. Infection-related stillbirths. Lancet 375:1482–90
    [Google Scholar]
  5. 5.  Zhou Y, Fisher SJ, Janatpour M, Genbacev O, Dejana E et al. 1997. Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion?. J. Clin. Invest. 99:2139–51
    [Google Scholar]
  6. 6.  Genbacev O, Zhou Y, Ludlow JW, Fisher SJ 1997. Regulation of human placental development by oxygen tension. Science 277:1669–72
    [Google Scholar]
  7. 7.  Pringle KG, Kind KL, Sferruzzi-Perri AN, Thompson JG, Roberts CT 2010. Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy. Hum. Reprod. Update 16:415–31
    [Google Scholar]
  8. 8.  Simister NE, Story CM, Chen HL, Hunt JS 1996. An IgG-transporting Fc receptor expressed in the syncytiotrophoblast of human placenta. Eur. J. Immunol. 26:1527–31
    [Google Scholar]
  9. 9.  Prakobphol A, Genbacev O, Gormley M, Kapidzic M, Fisher SJ 2006. A role for the L-selectin adhesion system in mediating cytotrophoblast emigration from the placenta. Dev. Biol. 298:107–17
    [Google Scholar]
  10. 10.  Drake PM, Red-Horse K, Fisher SJ 2004. Reciprocal chemokine receptor and ligand expression in the human placenta: implications for cytotrophoblast differentiation. Dev. Dyn. 229:877–85
    [Google Scholar]
  11. 11.  Red-Horse K, Drake PM, Fisher SJ 2004. Human pregnancy: the role of chemokine networks at the fetal-maternal interface. Expert Rev. Mol. Med. 2004:1–14
    [Google Scholar]
  12. 12.  Hess AP, Hamilton AE, Talbi S, Dosiou C, Nyegaard M et al. 2007. Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biol. Reprod. 76:102–17
    [Google Scholar]
  13. 13.  Damsky CH, Fisher SJ 1998. Trophoblast pseudo-vasculogenesis: faking it with endothelial adhesion receptors. Curr. Opin. Cell Biol. 10:660–66
    [Google Scholar]
  14. 14.  Zhou Y, Bellingard V, Feng KT, McMaster M, Fisher SJ 2003. Human cytotrophoblasts promote endothelial survival and vascular remodeling through secretion of Ang2, PlGF, and VEGF-C. Dev. Biol. 263:114–25
    [Google Scholar]
  15. 15.  Red-Horse K, Rivera J, Schanz A, Zhou Y, Winn V et al. 2006. Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation. J. Clin. Invest. 116:2643–52
    [Google Scholar]
  16. 16.  Ingman K, Cookson VJ, Jones CJ, Aplin JD 2010. Characterisation of Hofbauer cells in first and second trimester placenta: incidence, phenotype, survival in vitro and motility. Placenta 31:535–44
    [Google Scholar]
  17. 17.  Anteby EY, Natanson-Yaron S, Greenfield C, Goldman-Wohl D, Haimov-Kochman R et al. 2005. Human placental Hofbauer cells express sprouty proteins: a possible modulating mechanism of villous branching. Placenta 26:476–83
    [Google Scholar]
  18. 18.  Seval Y, Korgun ET, Demir R 2007. Hofbauer cells in early human placenta: possible implications in vasculogenesis and angiogenesis. Placenta 28:841–45
    [Google Scholar]
  19. 19.  Bockle BC, Solder E, Kind S, Romani N, Sepp NT 2008. DC-SIGN+ CD163+ macrophages expressing hyaluronan receptor LYVE-1 are located within chorion villi of the placenta. Placenta 29:187–92
    [Google Scholar]
  20. 20.  Young OM, Tang Z, Niven-Fairchild T, Tadesse S, Krikun G et al. 2015. Toll-like receptor-mediated responses by placental Hofbauer cells (HBCs): a potential pro-inflammatory role for fetal M2 macrophages. Am. J. Reprod. Immunol. 73:22–35
    [Google Scholar]
  21. 21.  Starkey PM, Sargent IL, Redman CW 1988. Cell populations in human early pregnancy decidua: characterization and isolation of large granular lymphocytes by flow cytometry. Immunology 65:129–34
    [Google Scholar]
  22. 22.  Aldo PB, Racicot K, Craviero V, Guller S, Romero R, Mor G 2014. Trophoblast induces monocyte differentiation into CD14+/CD16+ macrophages. Am. J. Reprod. Immunol. 72:270–84
    [Google Scholar]
  23. 23.  Gustafsson C, Mjosberg J, Matussek A, Geffers R, Matthiesen L et al. 2008. Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype. PLOS ONE 3:e2078
    [Google Scholar]
  24. 24.  Houser BL, Tilburgs T, Hill J, Nicotra ML, Strominger JL 2011. Two unique human decidual macrophage populations. J. Immunol. 186:2633–42
    [Google Scholar]
  25. 25.  Co EC, Gormley M, Kapidzic M, Rosen DB, Scott MA et al. 2013. Maternal decidual macrophages inhibit NK cell killing of invasive cytotrophoblasts during human pregnancy. Biol. Reprod. 88:155
    [Google Scholar]
  26. 26.  Saito S, Nishikawa K, Morii T, Narita N, Enomoto M et al. 1994. A study of CD45RO, CD45RA and CD29 antigen expression on human decidual T cells in an early stage of pregnancy. Immunol. Lett. 40:193–97
    [Google Scholar]
  27. 27.  Slukvin II, Merkulova AA, Vodyanik MA, Chernyshov VP 1996. Differential expression of CD45RA and CD45RO molecules on human decidual and peripheral blood lymphocytes at early stage of pregnancy. Am. J. Reprod. Immunol. 35:16–22
    [Google Scholar]
  28. 28.  Red-Horse K 2008. Lymphatic vessel dynamics in the uterine wall. Placenta 29:Suppl. AS55–59
    [Google Scholar]
  29. 29.  Red-Horse K, Kapidzic M, Zhou Y, Feng KT, Singh H, Fisher SJ 2005. EPHB4 regulates chemokine-evoked trophoblast responses: a mechanism for incorporating the human placenta into the maternal circulation. Development 132:4097–106
    [Google Scholar]
  30. 30.  Hannan NJ, Evans J, Salamonsen LA 2011. Alternate roles for immune regulators: establishing endometrial receptivity for implantation. Expert Rev. Clin. Immunol. 7:789–802
    [Google Scholar]
  31. 31.  Underwood MA, Gilbert WM, Sherman MP 2005. Amniotic fluid: not just fetal urine anymore. J. Perinatol. 25:341–48
    [Google Scholar]
  32. 32.  Buhimschi CS, Bhandari V, Hamar BD, Bahtiyar MO, Zhao G et al. 2007. Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis. PLOS Med 4:e18
    [Google Scholar]
  33. 33.  Li H, Niederkorn JY, Neelam S, Mayhew E, Word RA et al. 2005. Immunosuppressive factors secreted by human amniotic epithelial cells. Invest. Ophthalmol. Vis. Sci. 46:900–7
    [Google Scholar]
  34. 34.  Keelan JA, Sato T, Mitchell MD 1997. Interleukin (IL)-6 and IL-8 production by human amnion: regulation by cytokines, growth factors, glucocorticoids, phorbol esters, and bacterial lipopolysaccharide. Biol. Reprod. 57:1438–44
    [Google Scholar]
  35. 35.  Gervasi MT, Romero R, Bracalente G, Erez O, Dong Z et al. 2012. Midtrimester amniotic fluid concentrations of interleukin-6 and interferon-gamma-inducible protein-10: evidence for heterogeneity of intra-amniotic inflammation and associations with spontaneous early (<32 weeks) and late (>32 weeks) preterm delivery. J. Perinat. Med. 40:329–43
    [Google Scholar]
  36. 36.  Iwasenko JM, Howard J, Arbuckle S, Graf N, Hall B et al. 2011. Human cytomegalovirus infection is detected frequently in stillbirths and is associated with fetal thrombotic vasculopathy. J. Infect. Dis. 203:1526–33
    [Google Scholar]
  37. 37.  Genbacev O, Vicovac L, Larocque N 2015. The role of chorionic cytotrophoblasts in the smooth chorion fusion with parietal decidua. Placenta 36:716–22
    [Google Scholar]
  38. 38.  Genbacev O, Donne M, Kapidzic M, Gormley M, Lamb J et al. 2011. Establishment of human trophoblast progenitor cell lines from the chorion. Stem Cells 29:1427–36
    [Google Scholar]
  39. 39.  Haller H, Tedesco F, Rukavina D, Radillo O, Gudelj L, Beer AE 1995. Decidual-trophoblast interactions: decidual lymphoid cell populations in basal and parietal decidua. J. Reprod. Immunol. 28:165–71
    [Google Scholar]
  40. 40.  Hobman TC 2013. Rubella virus. See Ref. 195 687–711
  41. 41.  Modrow S, Falke D, Truyen U, Schatzl H 2013. Viruses with single-stranded, positive-sense RNA genomes. Molecular Virology185–349 Berlin: Springer
    [Google Scholar]
  42. 42.  Trinh QD, Pham NTK, Takada K, Komine-Aizawa S, Hayakawa S 2018. Myelin oligodendrocyte glycoprotein-independent rubella infection of keratinocytes and resistance of first-trimester trophoblast cells to rubella virus in vitro. Viruses 10:23
    [Google Scholar]
  43. 43.  Lazar M, Perelygina L, Martines R, Greer P, Paddock CD et al. 2016. Immunolocalization and distribution of rubella antigen in fatal congenital rubella syndrome. EBioMedicine 3:86–92
    [Google Scholar]
  44. 44.  Baltimore RS, Nimkin K, Sparger KA, Pierce VM, Plotkin SA 2018. Case 4-2018: a newborn with thrombocytopenia, cataracts, and hepatosplenomegaly. N. Engl. J. Med. 378:564–72
    [Google Scholar]
  45. 45.  Toizumi M, Nguyen GT, Motomura H, Nguyen TH, Pham E et al. 2017. Sensory defects and developmental delay among children with congenital rubella syndrome. Sci. Rep. 7:46483
    [Google Scholar]
  46. 46.  Geyer H, Bauer M, Neumann J, Ludde A, Rennert P et al. 2016. Gene expression profiling of rubella virus infected primary endothelial cells of fetal and adult origin. Virol. J. 13:21
    [Google Scholar]
  47. 47.  Hubner D, Jahn K, Pinkert S, Bohnke J, Jung M et al. 2017. Infection of iPSC lines with miscarriage-associated coxsackievirus and measles virus and teratogenic rubella virus as a model for viral impairment of early human embryogenesis. ACS Infect. Dis. 3:886–97
    [Google Scholar]
  48. 48.  Best JM, Cooray S, Banatvala JE 2005. Rubella virus. Topley and Wilson's Microbiology and Microbial Infections, Vol. 2: Virology BWJ Mahy, V ter Meulen 959–92 London: Hodder Arnold. , 10th ed..
    [Google Scholar]
  49. 49.  Zhou Q, Wang Q, Shen H, Zhang Y, Zhang S et al. 2017. Rubella virus immunization status in preconception period among Chinese women of reproductive age: a nation-wide, cross-sectional study. Vaccine 35:3076–81
    [Google Scholar]
  50. 50.  Vynnycky E, Adams EJ, Cutts FT, Reef SE, Navar AM et al. 2016. Using seroprevalence and immunisation coverage data to estimate the global burden of congenital rubella syndrome, 1996–2010: a systematic review. PLOS ONE 11:e0149160
    [Google Scholar]
  51. 51.  Young MK, Cripps AW, Nimmo GR, van Driel ML 2015. Post-exposure passive immunisation for preventing rubella and congenital rubella syndrome. Cochrane Database Syst. Rev.CD010586
    [Google Scholar]
  52. 52.  Perelygina L, Hautala T, Seppanen M, Adebayo A, Sullivan KE, Icenogle J 2017. Inhibition of rubella virus replication by the broad-spectrum drug nitazoxanide in cell culture and in a patient with a primary immune deficiency. Antiviral Res 147:58–66
    [Google Scholar]
  53. 53.  Qiu J, Soderlund-Venermo M, Young NS 2017. Human parvoviruses. Clin. Microbiol. Rev. 30:43–113
    [Google Scholar]
  54. 54.  Berns KI, Parrish CR 2013. Parvoviridae See Ref. 195 1768–91
    [Google Scholar]
  55. 55.  Cossart YE 1975. A new particulate antigen present in serum. Dev. Biol. Stand. 30:444–48
    [Google Scholar]
  56. 56.  Anderson MJ, Jones SE, Fisher-Hoch SP, Lewis E, Hall SM et al. 1983. Human parvovirus, the cause of erythema infectiosum (fifth disease)?. Lancet 1:1378
    [Google Scholar]
  57. 57.  Brown T, Anand A, Ritchie LD, Clewley JP, Reid TM 1984. Intrauterine parvovirus infection associated with hydrops fetalis. Lancet 2:1033–34
    [Google Scholar]
  58. 58.  Wong S, Zhi N, Filippone C, Keyvanfar K, Kajigaya S et al. 2008. Ex vivo-generated CD36+ erythroid progenitors are highly permissive to human parvovirus B19 replication. J. Virol. 82:2470–76
    [Google Scholar]
  59. 59.  Jordan JA, DeLoia JA 1999. Globoside expression within the human placenta. Placenta 20:103–8
    [Google Scholar]
  60. 60.  Weigel-Kelley KA, Yoder MC, Srivastava A 2003. α5β1 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of β1 integrin for viral entry. Blood 102:3927–33
    [Google Scholar]
  61. 61.  Munakata Y, Saito-Ito T, Kumura-Ishii K, Huang J, Kodera T et al. 2005. Ku80 autoantigen as a cellular coreceptor for human parvovirus B19 infection. Blood 106:3449–56
    [Google Scholar]
  62. 62.  Bonsch C, Zuercher C, Lieby P, Kempf C, Ros C 2010. The globoside receptor triggers structural changes in the B19 virus capsid that facilitate virus internalization. J. Virol. 84:11737–46
    [Google Scholar]
  63. 63.  Pasquinelli G, Bonvicini F, Foroni L, Salfi N, Gallinella G 2009. Placental endothelial cells can be productively infected by parvovirus B19. J. Clin. Virol. 44:33–38
    [Google Scholar]
  64. 64.  Watt AP, Brown M, Pathiraja M, Anbazhagan A, Coyle PV 2013. The lack of routine surveillance of parvovirus B19 infection in pregnancy prevents an accurate understanding of this regular cause of fetal loss and the risks posed by occupational exposure. J. Med. Microbiol. 62:86–92
    [Google Scholar]
  65. 65.  Bonvicini F, Puccetti C, Salfi NC, Guerra B, Gallinella G et al. 2011. Gestational and fetal outcomes in B19 maternal infection: a problem of diagnosis. J. Clin. Microbiol. 49:3514–18
    [Google Scholar]
  66. 66.  Bonvicini F, Bua G, Gallinella G 2017. Parvovirus B19 infection in pregnancy-awareness and opportunities. Curr. Opin. Virol. 27:8–14
    [Google Scholar]
  67. 67.  Enders M, Klingel K, Weidner A, Baisch C, Kandolf R et al. 2010. Risk of fetal hydrops and non-hydropic late intrauterine fetal death after gestational parvovirus B19 infection. J. Clin. Virol. 49:163–68
    [Google Scholar]
  68. 68.  Lindenburg IT, van Kamp IL, Oepkes D 2014. Intrauterine blood transfusion: current indications and associated risks. Fetal Diagn. Ther. 36:263–71
    [Google Scholar]
  69. 69.  Weiffenbach J, Bald R, Gloning KP, Minderer S, Gartner BC et al. 2012. Serological and virological analysis of maternal and fetal blood samples in prenatal human parvovirus B19 infection. J. Infect. Dis. 205:782–88
    [Google Scholar]
  70. 70.  Zerboni L, Sen N, Oliver SL, Arvin AM 2014. Molecular mechanisms of varicella zoster virus pathogenesis. Nat. Rev. Microbiol. 12:197–210
    [Google Scholar]
  71. 71.  Arvin AM, Golden D 2013. Varicella-zoster virus. See Ref. 195 2015–57
  72. 72.  Arvin AM, Moffat JF, Sommer M, Oliver S, Che X et al. 2010. Varicella-zoster virus T cell tropism and the pathogenesis of skin infection. Curr. Top. Microbiol. Immunol. 342:189–209
    [Google Scholar]
  73. 73.  Seward JF, Watson BM, Peterson CL, Mascola L, Pelosi JW et al. 2002. Varicella disease after introduction of varicella vaccine in the United States, 1995–2000. JAMA 287:606–11
    [Google Scholar]
  74. 74.  Ahn KH, Park YJ, Hong SC, Lee EH, Lee JS et al. 2016. Congenital varicella syndrome: a systematic review. J. Obstet. Gynecol. 36:563–66
    [Google Scholar]
  75. 75.  Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M 1994. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet 343:1548–51
    [Google Scholar]
  76. 76.  Paryani SG, Arvin AM 1986. Intrauterine infection with varicella-zoster virus after maternal varicella. N. Engl. J. Med. 314:1542–46
    [Google Scholar]
  77. 77.  Nikkels AF, Delbecque K, Pierard GE, Wienkotter B, Schalasta G, Enders M 2005. Distribution of varicella-zoster virus DNA and gene products in tissues of a first-trimester varicella-infected fetus. J. Infect. Dis. 191:540–45
    [Google Scholar]
  78. 78.  Sen N, Mukherjee G, Sen A, Bendall SC, Sung P et al. 2014. Single-cell mass cytometry analysis of human tonsil T cell remodeling by varicella zoster virus. Cell Rep 8:633–45
    [Google Scholar]
  79. 79.  Gershon AA, Gershon MD 2010. Perspectives on vaccines against varicella-zoster virus infections. Curr. Top. Microbiol. Immunol. 342:359–72
    [Google Scholar]
  80. 80.  Wilson E, Goss MA, Marin M, Shields KE, Seward JF et al. 2008. Varicella vaccine exposure during pregnancy: data from 10 years of the pregnancy registry. J. Infect. Dis. 197:Suppl. 2S178–84
    [Google Scholar]
  81. 81.  Mocarski ES, Shenk T, Griffiths PD, Pass RF 2013. Cytomegaloviruses. See Ref. 195 1960–2014
  82. 82.  Colugnati FA, Staras SA, Dollard SC, Cannon MJ 2007. Incidence of cytomegalovirus infection among the general population and pregnant women in the United States. BMC Infect. Dis. 7:71
    [Google Scholar]
  83. 83.  Kenneson A, Cannon MJ 2007. Review and meta-analysis of the epidemiology of congenital cyto-megalovirus (CMV) infection. Rev. Med. Virol. 17:253–76
    [Google Scholar]
  84. 84.  Boppana SB, Ross SA, Shimamura M, Palmer AL, Ahmed A et al. 2011. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N. Engl. J. Med. 364:2111–18
    [Google Scholar]
  85. 85.  Enders G, Daiminger A, Bader U, Exler S, Enders M 2011. Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J. Clin. Virol. 52:244–46
    [Google Scholar]
  86. 86.  Rosenthal LS, Fowler KB, Boppana SB, Britt WJ, Pass RF et al. 2009. Cytomegalovirus shedding and delayed sensorineural hearing loss: results from longitudinal follow-up of children with congenital infection. Pediatr. Infect. Dis. J. 28:515–20
    [Google Scholar]
  87. 87.  Revello MG, Fabbri E, Furione M, Zavattoni M, Lilleri D et al. 2011. Role of prenatal diagnosis and counseling in the management of 735 pregnancies complicated by primary human cytomegalovirus infection: a 20-year experience. J. Clin. Virol. 50:303–7
    [Google Scholar]
  88. 88.  Yamamoto AY, Mussi-Pinhata MM, Boppana SB, Novak Z, Wagatsuma VM et al. 2010. Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population. Am. J. Obstet. Gynecol. 202:297.e1–8
    [Google Scholar]
  89. 89.  Dollard SC, Schleiss MR, Grosse SD 2010. Public health and laboratory considerations regarding newborn screening for congenital cytomegalovirus. J. Inherit. Metab. Dis. 33:S249–54
    [Google Scholar]
  90. 90.  Enders G, Daiminger A, Bader U, Exler S, Schimpf Y, Enders M 2013. The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy. J. Clin. Virol. 56:102–7
    [Google Scholar]
  91. 91.  Dollard SC, Staras SA, Amin MM, Schmid DS, Cannon MJ 2011. National prevalence estimates for cytomegalovirus IgM and IgG avidity and association between high IgM antibody titer and low IgG avidity. Clin. Vaccine Immunol. 18:1895–99
    [Google Scholar]
  92. 92.  Ross SA, Ahmed A, Palmer AL, Michaels MG, Sanchez PJ et al. 2014. Detection of congenital cyto-megalovirus infection by real-time polymerase chain reaction analysis of saliva or urine specimens. J. Infect. Dis. 210:1415–18
    [Google Scholar]
  93. 93.  Garcia AG, Fonseca EF, Marques RL, Lobato YY 1989. Placental morphology in cytomegalovirus infection. Placenta 10:1–18
    [Google Scholar]
  94. 94.  Muhlemann K, Miller RK, Metlay L, Menegus MA 1992. Cytomegalovirus infection of the human placenta: an immunocytochemical study. Hum. Pathol. 23:1234–37
    [Google Scholar]
  95. 95.  Sinzger C, Müntefering H, Löning T, Stöss H, Plachter B, Jahn G 1993. Cell types infected in human cytomegalovirus placentitis identified by immunohistochemical double staining. Virchows Arch. A 423:249–56
    [Google Scholar]
  96. 96.  Pereira L, Petitt M, Fong A, Tsuge M, Tabata T et al. 2014. Intrauterine growth restriction caused by underlying congenital cytomegalovirus infection. J. Infect. Dis. 209:1573–84
    [Google Scholar]
  97. 97.  Tabata T, Petitt M, Fang-Hoover J, Zydek M, Pereira L 2016. Persistent cytomegalovirus infection in amniotic membranes of the human placenta. Am. J. Pathol. 186:2970–86
    [Google Scholar]
  98. 98.  Kondo K, Kaneshima H, Mocarski ES 1994. Human cytomegalovirus latent infection of granulocyte-macrophage progenitors. PNAS 91:11879–83
    [Google Scholar]
  99. 99.  Soderberg-Naucler C, Streblow DN, Fish KN, Allan-Yorke J, Smith PP, Nelson JA 2001. Reactivation of latent human cytomegalovirus in CD14+ monocytes is differentiation dependent. J. Virol. 75:7543–54
    [Google Scholar]
  100. 100.  Hargett D, Shenk TE 2010. Experimental human cytomegalovirus latency in CD14+ monocytes. PNAS 107:20039–44
    [Google Scholar]
  101. 101.  Noriega VM, Haye KK, Kraus TA, Kowalsky SR, Ge Y et al. 2014. Human cytomegalovirus modulates monocyte-mediated innate immune responses during short-term experimental latency in vitro. J. Virol. 88:9391–405
    [Google Scholar]
  102. 102.  Pereira L, Maidji E, McDonagh S, Genbacev O, Fisher S 2003. Human cytomegalovirus transmission from the uterus to the placenta correlates with the presence of pathogenic bacteria and maternal immunity. J. Virol. 77:13301–14
    [Google Scholar]
  103. 103.  Weisblum Y, Panet A, Haimov-Kochman R, Wolf DG 2014. Models of vertical cytomegalovirus (CMV) transmission and pathogenesis. Semin. Immunopathol. 36:615–25
    [Google Scholar]
  104. 104.  Weisblum Y, Oiknine-Djian E, Vorontsov OM, Haimov-Kochman R, Zakay-Rones Z et al. 2017. Zika virus infects early- and midgestation human maternal decidual tissues, inducing distinct innate tissue responses in the maternal-fetal interface. J. Virol. 91:e01905–16
    [Google Scholar]
  105. 105.  Avdic S, McSharry BP, Steain M, Poole E, Sinclair J et al. 2016. Human cytomegalovirus-encoded human interleukin-10 (IL-10) homolog amplifies its immunomodulatory potential by upregulating human IL-10 in monocytes. J. Virol. 90:3819–27
    [Google Scholar]
  106. 106.  Avdic S, Cao JZ, McSharry BP, Clancy LE, Brown R et al. 2013. Human cytomegalovirus interleukin-10 polarizes monocytes toward a deactivated M2c phenotype to repress host immune responses. J. Virol. 87:10273–82
    [Google Scholar]
  107. 107.  McDonagh S, Maidji E, Ma W, Chang HT, Fisher S, Pereira L 2004. Viral and bacterial pathogens at the maternal-fetal interface. J. Infect. Dis. 190:826–34
    [Google Scholar]
  108. 108.  Pereira L, Maidji E, McDonagh S, Tabata T 2005. Insights into viral transmission at the uterine-placental interface. Trends Microbiol 13:164–74
    [Google Scholar]
  109. 109.  Halwachs-Baumann G, Wilders-Truschnig M, Desoye G, Hahn T, Kiesel L et al. 1998. Human trophoblast cells are permissive to the complete replicative cycle of human cytomegalovirus. J. Virol. 72:7598–602
    [Google Scholar]
  110. 110.  Fisher S, Genbacev O, Maidji E, Pereira L 2000. Human cytomegalovirus infection of placental cytotrophoblasts in vitro and in utero: implications for transmission and pathogenesis. J. Virol. 74:6808–20
    [Google Scholar]
  111. 111.  Yamamoto-Tabata T, McDonagh S, Chang HT, Fisher S, Pereira L 2004. Human cytomegalovirus interleukin-10 downregulates metalloproteinase activity and impairs endothelial cell migration and placental cytotrophoblast invasiveness in vitro. J. Virol. 78:2831–40
    [Google Scholar]
  112. 112.  Tabata T, McDonagh S, Kawakatsu H, Pereira L 2007. Cytotrophoblasts infected with a pathogenic human cytomegalovirus strain dysregulate cell-matrix and cell-cell adhesion molecules: a quantitative analysis. Placenta 28:527–37
    [Google Scholar]
  113. 113.  Tabata T, Petitt M, Zydek M, Fang-Hoover J, Larocque N et al. 2015. Human cytomegalovirus infection interferes with the maintenance and differentiation of trophoblast progenitor cells of the human placenta. J. Virol. 89:5134–47
    [Google Scholar]
  114. 114.  Zydek M, Petitt M, Fang-Hoover J, Adler B, Kauvar LM et al. 2014. HCMV infection of human trophoblast progenitor cells of the placenta is neutralized by a human monoclonal antibody to glycoprotein B and not by antibodies to the pentamer complex. Viruses 6:1346–64
    [Google Scholar]
  115. 115.  Maidji E, Nigro G, Tabata T, McDonagh S, Nozawa N et al. 2010. Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection. Am. J. Pathol. 177:1298–310
    [Google Scholar]
  116. 116.  Ross DS, Victor M, Sumartojo E, Cannon MJ 2008. Women's knowledge of congenital cytomegalovirus: results from the 2005 HealthStyles survey. J. Women's Health 17:849–58
    [Google Scholar]
  117. 117.  Cannon MJ, Davis KF 2005. Washing our hands of the congenital cytomegalovirus disease epidemic. BMC Public Health 5:70
    [Google Scholar]
  118. 118.  Revello MG, Tibaldi C, Masuelli G, Frisina V, Sacchi A et al. 2015. Prevention of primary cytomegalovirus infection in pregnancy. EBioMedicine 2:1205–10
    [Google Scholar]
  119. 119.  Adler SP 2012. Editorial commentary: primary maternal cytomegalovirus infection during pregnancy: Do we have a treatment option?. Clin. Infect. Dis. 55:504–6
    [Google Scholar]
  120. 120.  Nozawa N, Fang-Hoover J, Tabata T, Maidji E, Pereira L 2009. Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal circulation enriched in the fetal bloodstream. J. Clin. Virol. 46:Suppl. 4S58–63
    [Google Scholar]
  121. 121.  Nigro G, Adler SP, La Torre R, Best AM 2005. Passive immunization during pregnancy for congenital cytomegalovirus infection. N. Engl. J. Med. 353:1350–62
    [Google Scholar]
  122. 122.  Buxmann H, Stackelberg OM, Schlosser RL, Enders G, Gonser M et al. 2012. Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J. Perinat. Med. 40:439–46
    [Google Scholar]
  123. 123.  Revello MG, Lazzarotto T, Guerra B, Spinillo A, Ferrazzi E et al. 2014. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N. Engl. J. Med. 370:1316–26
    [Google Scholar]
  124. 124.  Fouts AE, Chan P, Stephan JP, Vandlen R, Feierbach B 2012. Antibodies against the gH/gL/UL128/UL130/UL131 complex comprise the majority of the anti-cytomegalovirus (anti-CMV) neutralizing antibody response in CMV hyperimmune globulin. J. Virol. 86:7444–47
    [Google Scholar]
  125. 125.  Lilleri D, Kabanova A, Revello MG, Percivalle E, Sarasini A et al. 2013. Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection. PLOS ONE 8:e59863
    [Google Scholar]
  126. 126.  Wang X, Xu Y, Scott DE, Murata H, Struble EB 2017. Binding and neutralizing anti-cytomegalovirus activities in immune globulin products. Biologicals 50:35–41
    [Google Scholar]
  127. 127.  Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R 2004. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin. Infect. Dis. 39:233–39
    [Google Scholar]
  128. 128.  Ha S, Li F, Troutman MC, Freed DC, Tang A et al. 2017. Neutralization of diverse human cytomegalovirus strains conferred by antibodies targeting viral gH/gL/pUL128-131 pentameric complex. J. Virol. 91:e02033
    [Google Scholar]
  129. 129.  Schleiss MR, Permar SR, Plotkin SA 2017. Progress toward development of a vaccine against congenital cytomegalovirus infection. Clin. Vaccine Immunol. 24:e00268
    [Google Scholar]
  130. 130.  Haddow AJ, Williams MC, Woodall JP, Simpson DI, Goma LK 1964. Twelve isolations of Zika virus from Aedes (Stegomyia) africanus (theobald) taken in and above a Uganda forest. Bull. World Health Organ. 31:57–69
    [Google Scholar]
  131. 131.  Faria NR, Quick J, Claro IM, Theze J, de Jesus JG et al. 2017. Establishment and cryptic transmission of Zika virus in Brazil and the Americas. Nature 546:406–10
    [Google Scholar]
  132. 132.  Herrera BB, Chang CA, Hamel DJ, Mboup S, Ndiaye D et al. 2017. Continued transmission of Zika virus in humans in West Africa, 1992–2016. J. Infect. Dis. 215:1546–50
    [Google Scholar]
  133. 133.  Duffy MR, Chen T-H, Hancock WT, Powers AM, Kool JL et al. 2009. Zika virus outbreak on Yap Island, Federated States of Micronesia. N. Engl. J. Med. 360:2536–43
    [Google Scholar]
  134. 134.  Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C et al. 2016. Guillain-Barre syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 387:1531–39
    [Google Scholar]
  135. 135.  Tognarelli J, Ulloa S, Villagra E, Lagos J, Aguayo C et al. 2016. A report on the outbreak of Zika virus on Easter Island, South Pacific, 2014. Arch. Virol. 161:665–68
    [Google Scholar]
  136. 136.  Haddow AD, Schuh AJ, Yasuda CY, Kasper MR, Heang V et al. 2012. Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage. PLOS Negl. Trop. Dis. 6:e1477
    [Google Scholar]
  137. 137.  Aliota MT, Bassit L, Bradrick SS, Cox B, Garcia-Blanco MA et al. 2017. Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network. Antivir. Res. 144:223–46
    [Google Scholar]
  138. 138.  Pierson TC, Diamond MS 2013. Flaviviruses. See Ref. 195 747–94
  139. 139.  Lindenbach BD, Murray CL, Thiel HJ, Rice CM 2013. Flaviviridae. See Ref. 195 712–46
  140. 140.  Martines RB, Bhatnagar J, Keating MK, Silva-Flannery L, Muehlenbachs A et al. 2016. Notes from the field: evidence of Zika virus infection in brain and placental tissues from two congenitally infected newborns and two fetal losses—Brazil, 2015. Morb. Mortal. Wkly. Rep. 65:159–60
    [Google Scholar]
  141. 141.  Styczynski AR, Malta J, Krow-Lucal ER, Percio J, Nobrega ME et al. 2017. Increased rates of Guillain-Barre syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil. PLOS Negl. Trop. Dis. 11:e0005869
    [Google Scholar]
  142. 142.  Martines RB, Bhatnagar J, de Oliveira Ramos AM, Davi HP, Iglezias SD et al. 2016. Pathology of congenital Zika syndrome in Brazil: a case series. Lancet 388:898–904
    [Google Scholar]
  143. 143.  Melo AS, Aguiar RS, Amorim MM, Arruda MB, Melo FO et al. 2016. Congenital Zika virus infection: beyond neonatal microcephaly. JAMA Neurol 73:1407–16
    [Google Scholar]
  144. 144.  Russell K, Hills SL, Oster AM, Porse CC, Danyluk G et al. 2017. Male-to-female sexual transmission of Zika Virus—United States, January–April 2016. Clin. Infect. Dis. 64:211–13
    [Google Scholar]
  145. 145.  Costa F, Sarno M, Khouri R, de Paula Freitas B, Siqueira I et al. 2016. Emergence of congenital Zika syndrome: viewpoint from the front lines. Ann. Intern. Med. 164:689–91
    [Google Scholar]
  146. 146.  Driggers RW, Ho CY, Korhonen EM, Kuivanen S, Jaaskelainen AJ et al. 2016. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N. Engl. J. Med. 374:2142–51
    [Google Scholar]
  147. 147.  Mlakar J, Korva M, Tul N, Popovic M, Poljsak-Prijatelj M et al. 2016. Zika virus associated with microcephaly. N. Engl. J. Med. 374:951–58
    [Google Scholar]
  148. 148.  Delaney A, Mai C, Smoots A, Cragan J, Ellington S et al. 2018. Population-based surveillance of birth defects potentially related to Zika virus infection—15 states and U.S. territories, 2016. Morb. Mortal. Wkly. Rep. 67:91–96
    [Google Scholar]
  149. 149.  Shapiro-Mendoza CK, Rice ME, Galang RR, Fulton AC, VanMaldeghem K et al. 2017. Pregnancy outcomes after maternal Zika virus infection during pregnancy—U.S. territories, January 1, 2016–April 25, 2017. Morb. Mortal. Wkly. Rep. 66:615–21
    [Google Scholar]
  150. 150.  Jaenisch T, Rosenberger KD, Brito C, Brady O, Brasil P, Marques ET 2017. Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016. Bull. World Health Organ. 95:191–98
    [Google Scholar]
  151. 151.  Snyder RE, Boone CE, Cardoso CA, Aguiar-Alves F, Neves FP, Riley LW 2017. Zika: a scourge in urban slums. PLOS Negl. Trop. Dis. 11:e0005287
    [Google Scholar]
  152. 152.  Ferguson NM, Cucunuba ZM, Dorigatti I, Nedjati-Gilani GL, Donnelly CA et al. 2016. Countering the Zika epidemic in Latin America. Science 353:353–54
    [Google Scholar]
  153. 153.  Faye O, Freire CCM, Iamarino A, Faye O, de Oliveira JVC et al. 2014. Molecular evolution of Zika virus during its emergence in the 20th century. PLOS Negl. Trop. Dis. 8:e2636
    [Google Scholar]
  154. 154.  Puerta-Guardo H, Glasner DR, Harris E 2016. Dengue virus NS1 disrupts the endothelial glycocalyx, leading to hyperpermeability. PLOS Pathog 12:e1005738
    [Google Scholar]
  155. 155.  Glasner DR, Ratnasiri K, Puerta-Guardo H, Espinosa DA, Beatty PR, Harris E 2017. Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components. PLOS Pathog 13:e1006673
    [Google Scholar]
  156. 156.  Modhiran N, Watterson D, Muller DA, Panetta AK, Sester DP et al. 2015. Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity. Sci. Transl. Med. 7:304ra142
    [Google Scholar]
  157. 157.  Brown WC, Akey DL, Konwerski JR, Tarrasch JT, Skiniotis G et al. 2016. Extended surface for membrane association in Zika virus NS1 structure. Nat. Struct. Mol. Biol. 23:865–67
    [Google Scholar]
  158. 158.  Song H, Qi J, Haywood J, Shi Y, Gao GF 2016. Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses. Nat. Struct. Mol. Biol. 23:456–58
    [Google Scholar]
  159. 159.  Xu X, Song H, Qi J, Liu Y, Wang H et al. 2016. Contribution of intertwined loop to membrane association revealed by Zika virus full-length NS1 structure. EMBO J 35:2170–78
    [Google Scholar]
  160. 160.  Liu Y, Liu J, Du S, Shan C, Nie K et al. 2017. Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature 545:482–86
    [Google Scholar]
  161. 161.  Waggoner JJ, Gresh L, Vargas MJ, Ballesteros G, Tellez Y et al. 2016. Viremia and clinical presentation in Nicaraguan patients infected with Zika virus, chikungunya virus, and dengue virus. Clin. Infect. Dis. 63:1584–90
    [Google Scholar]
  162. 162.  Brasil P, Pereira JP Jr., Moreira ME, Ribeiro Nogueira RM, Damasceno L et al. 2016. Zika virus infection in pregnant women in Rio de Janeiro. N. Engl. J. Med. 375:2321–34
    [Google Scholar]
  163. 163.  Reagan-Steiner S, Simeone R, Simon E, Bhatnagar J, Oduyebo T et al. 2017. Evaluation of placental and fetal tissue specimens for Zika virus infection—50 states and District of Columbia, January–December, 2016. Morb. Mortal. Wkly. Rep. 66:636–43
    [Google Scholar]
  164. 164.  Balmaseda A, Stettler K, Medialdea-Carrera R, Collado D, Jin X et al. 2017. Antibody-based assay discriminates Zika virus infection from other flaviviruses. PNAS 114:8384–89
    [Google Scholar]
  165. 165.  Stettler K, Beltramello M, Espinosa DA, Graham V, Cassotta A et al. 2016. Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection. Science 353:823–26
    [Google Scholar]
  166. 166.  Kam YW, Lee CY, Teo TH, Howland SW, Amrun SN et al. 2017. Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections. JCI Insight 2:e92428
    [Google Scholar]
  167. 167.  Dejnirattisai W, Supasa P, Wongwiwat W, Rouvinski A, Barba-Spaeth G et al. 2016. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with Zika virus. Nat. Immunol. 17:1102–8
    [Google Scholar]
  168. 168.  Halai UA, Nielsen-Saines K, Moreira ML, de Sequeira PC, Junior JPP et al. 2017. Maternal Zika virus disease severity, virus load, prior dengue antibodies, and their relationship to birth outcomes. Clin. Infect. Dis. 65:877–83
    [Google Scholar]
  169. 169.  Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Wang C et al. 2016. Zika virus targets different primary human placental cells, suggesting two routes for vertical transmission. Cell Host Microbe 20:155–66
    [Google Scholar]
  170. 170.  El Costa H, Gouilly J, Mansuy JM, Chen Q, Levy C et al. 2016. Zika virus reveals broad tissue and cell tropism during the first trimester of pregnancy. Sci. Rep. 6:35296
    [Google Scholar]
  171. 171.  Quicke KM, Bowen JR, Johnson EL, McDonald CE, Ma H et al. 2016. Zika virus infects human placental macrophages. Cell Host Microbe 20:83–90
    [Google Scholar]
  172. 172.  Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Harris E, Pereira L 2017. Zika virus replicates in proliferating cells in explants from first-trimester human placentas, potential sites for dissemination of infection. J. Infect. Dis. 27:48–56
    [Google Scholar]
  173. 173.  Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S et al. 2016. Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe 19:705–12
    [Google Scholar]
  174. 174.  Petitt M, Tabata T, Puerta-Guardo H, Harris E, Pereira L 2017. Zika virus infection of first-trimester human placentas: utility of an explant model of replication to evaluate correlates of immune protection ex vivo. Curr. Opin. Virol. 27:48–56
    [Google Scholar]
  175. 175.  Michlmayr D, Andrade P, Gonzalez K, Balmaseda A, Harris E 2017. CD14+ CD16+ monocytes are the main target of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua. Nat. Microbiol. 2:1462–70
    [Google Scholar]
  176. 176.  Foo SS, Chen W, Chan Y, Bowman JW, Chang LC et al. 2017. Asian Zika virus strains target CD14+ blood monocytes and induce M2-skewed immunosuppression during pregnancy. Nat. Microbiol. 2:1558–70
    [Google Scholar]
  177. 177.  Bowen JR, Quicke KM, Maddur MS, O'Neal JT, McDonald CE et al. 2017. Zika virus antagonizes type I interferon responses during infection of human dendritic cells. PLOS Pathog 13:e1006164
    [Google Scholar]
  178. 178.  Rosenberg AZ, Yu W, Hill DA, Reyes CA, Schwartz DA 2017. Placental pathology of Zika virus: Viral infection of the placenta induces villous stromal macrophage (Hofbauer cell) proliferation and hyperplasia. Arch. Pathol. Lab. Med. 141:43–48
    [Google Scholar]
  179. 179.  Jemielity S, Wang JJ, Chan YK, Ahmed AA, Li W et al. 2013. TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLOS Pathog 9:e1003232
    [Google Scholar]
  180. 180.  Richard AS, Zhang A, Park SJ, Farzan M, Zong M, Choe H 2015. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses. PNAS 112:14682–87
    [Google Scholar]
  181. 181.  Barouch DH, Thomas SJ, Michael NL 2017. Prospects for a Zika virus vaccine. Immunity 46:176–82
    [Google Scholar]
  182. 182.  Dowd KA, DeMaso CR, Pelc RS, Speer SD, Smith AR et al. 2016. Broadly neutralizing activity of Zika virus-immune sera identifies a single viral serotype. Cell Rep 16:1485–91
    [Google Scholar]
  183. 183.  Larocca RA, Abbink P, Peron JP, Zanotto PM, Iampietro MJ et al. 2016. Vaccine protection against Zika virus from Brazil. Nature 536:474–78
    [Google Scholar]
  184. 184.  Aid M, Abbink P, Larocca RA, Boyd M, Nityanandam R et al. 2017. Zika virus persistence in the central nervous system and lymph nodes of rhesus monkeys. Cell 169:610–20
    [Google Scholar]
  185. 185.  Hirsch AJ, Smith JL, Haese NN, Broeckel RM, Parkins CJ et al. 2017. Zika virus infection of rhesus macaques leads to viral persistence in multiple tissues. PLOS Pathog 13:e1006219
    [Google Scholar]
  186. 186.  Poland G, Kennedy R, Ovsyannikova I, Palacios R, Ho P, Kalil J 2018. Development of vaccines against Zika virus. Lancet Infect. Dis. 18:e211–19
    [Google Scholar]
  187. 187.  Emerson SU, Purcell RH 2013. Hepatitis E virus. See Ref. 195 2242–58
  188. 188.  Perez-Gracia MT, Suay-Garcia B, Mateos-Lindemann ML 2017. Hepatitis E and pregnancy: current state. Rev. Med. Virol. 27:e1929
    [Google Scholar]
  189. 189.  Sharma S, Kumar A, Kar P, Agarwal S, Ramji S et al. 2017. Risk factors for vertical transmission of hepatitis E virus infection. J. Viral Hepat. 24:1067–75
    [Google Scholar]
  190. 190.  Bose PD, Das BC, Hazam RK, Kumar A, Medhi S, Kar P 2014. Evidence of extrahepatic replication of hepatitis E virus in human placenta. J. Gen. Virol. 95:1266–71
    [Google Scholar]
  191. 191.  Bose PD, Das BC, Kumar A, Gondal R, Kumar D, Kar P 2011. High viral load and deregulation of the progesterone receptor signaling pathway: association with hepatitis E-related poor pregnancy outcome. J. Hepatol. 54:1107–13
    [Google Scholar]
  192. 192.  Aggarwal R 2010. The Global Prevalence of Hepatitis E Virus Infection: A Systematic Review Rep., Dep. Immun. Vaccines Biol, World Health Organ., Geneva
    [Google Scholar]
  193. 193. World Health Organ. 2017. Hepatitis E fact sheet Fact Sheet, World Health Organ. Geneva: http://www.who.int/mediacentre/factsheets/fs280/en/
    [Google Scholar]
  194. 194.  Kuniholm MH, Purcell RH, McQuillan GM, Engle RE, Wasley A, Nelson KE 2009. Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988–1994. J. Infect. Dis. 200:48–56
    [Google Scholar]
  195. 195.  Knipe DM, Howley PM, eds. 2013. Fields Virology Philadelphia, PA: Wolters Kluwer, Lippincott Williams & Wilkins. , 6th ed..
    [Google Scholar]
  196. 196.  Standring S 2005. Gray's Anatomy: The Anatomical Basis of Clinical Practice London: Churchill Livingstone. , 39th ed..
    [Google Scholar]
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