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Volume 23, Number 3—March 2017
Research

Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

Julu BhatnagarComments to Author , Demi B. Rabeneck, Roosecelis B. Martines, Sarah Reagan-Steiner, Yokabed Ermias, Lindsey B.C. Estetter, Tadaki Suzuki, Jana M. Ritter, M. Kelly Keating, Gillian Hale, Joy Gary, Atis Muehlenbachs, Amy J. Lambert, Robert Lanciotti, Titilope Oduyebo, Dana Meaney-Delman, Fernando Bolaños, Edgar Alberto Parra Saad, Wun-Ju Shieh, and Sherif Zaki
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (J. Bhatnagar, D.B. Rabeneck, R.B. Martines, S. Reagan-Steiner, Y. Ermias, L.B.C. Estetter, T. Suzuki, J. Ritter, M.K. Keating, G. Hale, J. Gary, A. Muehlenbachs, T. Oduyebo, D. Meaney-Delman, W. Shieh, S.R. Zaki); Centers for Disease Control and Prevention, Fort Collins, Colorado, USA (A. Lambert, R. Lanciotti); Patología Hospital Universitario de Neiva, Neiva, Colombia (F. Bolaños); Instituto Nacional de Salud, Bogota, Colombia (E.A. Parra Saad)

Main Article

Table 1

Oligonucleotide primers used for RT-PCR assays*

RT-PCR Primers Sequence, 5′→3′ Gene target Product size, bp Annealing temperature, °C Reference
Zika virus
 Forward AAG TAC ACA TAC CAA AAC AAA GTG GT NS5
 127
 56
 This study
Reverse
 TGT TAA GAG CGT AAG TGA CAA C
Zika virus
 Forward TGC CCA ACA CAA GGT GAA GC E
 209
 58
 This study
Reverse
 ACT GAC AGC ATT ATC CGG TAC TC
DENV1–4
 Forward AAG GAC TAG AGG TTA KAG GAG ACC C 3′ UTR
 110
 62
 (27)
Reverse
 GGC GYT CTG TGC CTG GAW TGA TG
CHIKV Forward TCA CTC CCT GTT GGA CTT GAT AGA PPG 126 55 (28)
Reverse TTG ACG AAC AGA GTT AGG AAC ATA CC

*CHIKV, chikungunya virus; DENV, dengue virus; E, envelope; NS, nonstructural; PPG, polyprotein gene; RT-PCR, reverse transcription PCR; UTR, untranslated region.

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References
  1. Hennessey  M, Fischer  M, Staples  JE. Zika virus spreads to new areas—region of the Americas, May 2015–January 2016. MMWR Morb Mortal Wkly Rep. 2016;65:55–8. DOIPubMedGoogle Scholar
  2. Rasmussen  SA, Jamieson  DJ, Honein  MA, Petersen  LR. Zika virus and birth defects—reviewing the evidence for causality. N Engl J Med. 2016;374:1981–7. DOIPubMedGoogle Scholar
  3. Cauchemez  S, Besnard  M, Bompard  P, Dub  T, Guillemette-Artur  P, Eyrolle-Guignot  D, et al. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet. 2016;387:2125–32. DOIPubMedGoogle Scholar
  4. Simeone  RM, Shapiro-Mendoza  CK, Meaney-Delman  D, Petersen  EE, Galang  RR, Oduyebo  T, et al.; Zika and Pregnancy Working Group. Possible Zika virus infection among pregnant women–United States and Territories, May 2016. MMWR Morb Mortal Wkly Rep. 2016;65:514–9. DOIPubMedGoogle Scholar
  5. Calvet  G, Aguiar  RS, Melo  AS, Sampaio  SA, de Filippis  I, Fabri  A, et al. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis. 2016;16:653–60. DOIPubMedGoogle Scholar
  6. Sarno  M, Sacramento  GA, Khouri  R, do Rosário  MS, Costa  F, Archanjo  G, et al. Zika virus infection and stillbirths: a case of hydrops fetalis, hydranencephaly and fetal demise. PLoS Negl Trop Dis. 2016;10:e0004517. DOIPubMedGoogle Scholar
  7. Brasil  P, Pereira  JP Jr, Raja Gabaglia  C, Damasceno  L, Wakimoto  M, Ribeiro Nogueira  RM, et al. Zika virus infection in pregnant women in Rio de Janeiro—preliminary report. N Engl J Med. 2016 Mar 4 [Epub ahead of print].;NEJMoa1602412. DOIPubMedGoogle Scholar
  8. Tang  H, Hammack  C, Ogden  SC, Wen  Z, Qian  X, Li  Y, et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell. 2016;18:587–90. DOIPubMedGoogle Scholar
  9. Cugola  FR, Fernandes  IR, Russo  FB, Freitas  BC, Dias  JL, Guimarães  KP, et al. The Brazilian Zika virus strain causes birth defects in experimental models. Nature. 2016;534:267–71.PubMedGoogle Scholar
  10. Li  C, Xu  D, Ye  Q, Hong  S, Jiang  Y, Liu  X, et al. Zika virus disrupts neural progenitor development and leads to microcephaly in mice. Cell Stem Cell. 2016;19:120–6. DOIPubMedGoogle Scholar
  11. Garcez  PP, Loiola  EC, Madeiro da Costa  R, Higa  LM, Trindade  P, Delvecchio  R, et al. Zika virus impairs growth in human neurospheres and brain organoids. Science. 2016;352:816–8. DOIPubMedGoogle Scholar
  12. Quicke  KM, Bowen  JR, Johnson  EL, McDonald  CE, Ma  H, O’Neal  JT, et al. Zika virus infects human placental macrophages. Cell Host Microbe. 2016;20:83–90. DOIPubMedGoogle Scholar
  13. Bayer  A, Lennemann  NJ, Ouyang  Y, Bramley  JC, Morosky  S, Marques  ET Jr, et al. Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe. 2016;19:705–12. DOIPubMedGoogle Scholar
  14. Miner  JJ, Cao  B, Govero  J, Smith  AM, Fernandez  E, Cabrera  OH, et al. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell. 2016;165:1081–91. DOIPubMedGoogle Scholar
  15. Adibi  JJ, Zhao  Y, Cartus  AR, Gupta  P, Davidson  LA. Placental mechanics in the Zika-microcephaly relationship. Cell Host Microbe. 2016;20:9–11. DOIPubMedGoogle Scholar
  16. Aliota  MT, Caine  EA, Walker  EC, Larkin  KE, Camacho  E, Osorio  JE, et al. Characterization of lethal Zika virus infection in AG129 mice. PLoS Negl Trop Dis. 2016;10. DOIGoogle Scholar
  17. Pulvers  JN, Bryk  J, Fish  JL, Wilsch-Bräuninger  M, Arai  Y, Schreier  D, et al. Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline. Proc Natl Acad Sci U S A. 2010;107:16595–600. DOIPubMedGoogle Scholar
  18. Martines  RB, Bhatnagar  J, Keating  MK, Silva-Flannery  L, Muehlenbachs  A, Gary  J, et al. 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. MMWR Morb Mortal Wkly Rep. 2016;65:159–60. DOIPubMedGoogle Scholar
  19. Martines  RB, Bhatnagar  J, de Oliveira Ramos  AM, Davi  HP, Iglezias  SD, Kanamura  CT, et al. Pathology of congenital Zika syndrome in Brazil: a case series. Lancet. 2016;388:898–904. DOIPubMedGoogle Scholar
  20. Mlakar  J, Korva  M, Tul  N, Popović  M, Poljšak-Prijatelj  M, Mraz  J, et al. Zika virus associated with microcephaly. N Engl J Med. 2016;374:951–8. DOIPubMedGoogle Scholar
  21. Driggers  RW, Ho  CY, Korhonen  EM, Kuivanen  S, Jääskeläinen  AJ, Smura  T, et al. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med. 2016;374:2142–51. DOIPubMedGoogle Scholar
  22. Kourtis  AP, Read  JS, Jamieson  DJ. Pregnancy and infection. N Engl J Med. 2014;370:2211–8. DOIPubMedGoogle Scholar
  23. Lanciotti  RS, Kosoy  OL, Laven  JJ, Velez  JO, Lambert  AJ, Johnson  AJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14:1232–9. DOIPubMedGoogle Scholar
  24. Karwowski  MP, Nelson  JM, Staples  JE, Fischer  M, Fleming-Dutra  KE, Villanueva  J, et al. Zika virus disease: a CDC update for pediatric health care providers. Pediatrics. 2016;137:pii:e20160621. DOIPubMedGoogle Scholar
  25. Rabe  IB, Staples  JE, Villanueva  J, Hummel  KB, Johnson  JA, Rose  L, et al.; MTS. Interim guidance for interpretation of Zika virus antibody test results. MMWR Morb Mortal Wkly Rep. 2016;65:543–6. DOIPubMedGoogle Scholar
  26. Bhatnagar  J, Blau  DM, Shieh  WJ, Paddock  CD, Drew  C, Liu  L, et al. Molecular detection and typing of dengue viruses from archived tissues of fatal cases by rt-PCR and sequencing: diagnostic and epidemiologic implications. Am J Trop Med Hyg. 2012;86:335–40. DOIPubMedGoogle Scholar
  27. Callahan  JD, Wu  SJ, Dion-Schultz  A, Mangold  BE, Peruski  LF, Watts  DM, et al. Development and evaluation of serotype- and group-specific fluorogenic reverse transcriptase PCR (TaqMan) assays for dengue virus. J Clin Microbiol. 2001;39:4119–24. DOIPubMedGoogle Scholar
  28. Lanciotti  RS, Kosoy  OL, Laven  JJ, Panella  AJ, Velez  JO, Lambert  AJ, et al. Chikungunya virus in US travelers returning from India, 2006. Emerg Infect Dis. 2007;13:764–7. DOIPubMedGoogle Scholar
  29. Nakajima  N, Hata  S, Sato  Y, Tobiume  M, Katano  H, Kaneko  K, et al. The first autopsy case of pandemic influenza (A/H1N1pdm) virus infection in Japan: detection of a high copy number of the virus in type II alveolar epithelial cells by pathological and virological examination. Jpn J Infect Dis. 2010;63:67–71.PubMedGoogle Scholar
  30. Wang  F, Flanagan  J, Su  N, Wang  LC, Bui  S, Nielson  A, et al. RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J Mol Diagn. 2012;14:22–9. DOIPubMedGoogle Scholar
  31. Nowakowski  TJ, Pollen  AA, Di Lullo  E, Sandoval-Espinosa  C, Bershteyn  M, Kriegstein  AR. Expression analysis highlights AXL as a candidate Zika virus entry receptor in neural stem cells. Cell Stem Cell. 2016;18:591–6. DOIPubMedGoogle Scholar
  32. Lazar  M, Perelygina  L, Martines  R, Greer  P, Paddock  CD, Peltecu  G, et al. Immunolocalization and distribution of rubella antigen in fatal congenital rubella syndrome. EBioMedicine. 2015;3:86–92. DOIPubMedGoogle Scholar
  33. Ritter  JM, Martines  RB, Zaki  SR. Zika virus: pathology from the pandemic. Arch Pathol Lab Med. 2016 Oct 5 [Epub ahead of print].
  34. Halstead  SB. Antibody, macrophages, dengue virus infection, shock, and hemorrhage: a pathogenetic cascade. Rev Infect Dis. 1989;11(Suppl 4):S830–9. DOIPubMedGoogle Scholar
  35. Winchester  SA, Varga  Z, Parmar  D, Brown  KE. Persistent intraocular rubella infection in a patient with Fuchs’ uveitis and congenital rubella syndrome. J Clin Microbiol. 2013;51:1622–4. DOIPubMedGoogle Scholar
  36. O’Neill  JF. The ocular manifestations of congenital infection: a study of the early effect and long-term outcome of maternally transmitted rubella and toxoplasmosis. Trans Am Ophthalmol Soc. 1998;96:813–79.PubMedGoogle Scholar
  37. Appler  KK, Brown  AN, Stewart  BS, Behr  MJ, Demarest  VL, Wong  SJ, et al. Persistence of West Nile virus in the central nervous system and periphery of mice. PLoS One. 2010;5:e10649. DOIPubMedGoogle Scholar
  38. Bhatnagar  J, Guarner  J, Paddock  CD, Shieh  WJ, Lanciotti  RS, Marfin  AA, et al. Detection of West Nile virus in formalin-fixed, paraffin-embedded human tissues by RT-PCR: a useful adjunct to conventional tissue-based diagnostic methods. J Clin Virol. 2007;38:106–11. DOIPubMedGoogle Scholar
  39. Labadie  K, Larcher  T, Joubert  C, Mannioui  A, Delache  B, Brochard  P, et al. Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages. J Clin Invest. 2010;120:894–906. DOIPubMedGoogle Scholar
  40. Oliveira  DB, Almeida  FJ, Durigon  EL, Mendes  ÉA, Braconi  CT, Marchetti  I, et al. Prolonged shedding of Zika virus associated with congenital infection. N Engl J Med. 2016;375:1202–4. DOIPubMedGoogle Scholar

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