PMID- 27613665
OWN - NLM
STAT- MEDLINE
DCOM- 20171226
LR  - 20180403
IS  - 1600-0897 (Electronic)
IS  - 1046-7408 (Linking)
VI  - 76
IP  - 5
DP  - 2016 Nov
TI  - HSV-2 enhances ZIKV infection of the placenta and induces apoptosis in 
      first-trimester trophoblast cells.
PG  - 348-357
LID - 10.1111/aji.12578 [doi]
AB  - PROBLEM: Zika virus (ZIKV) has gained public concern for its association with 
      microcephaly in infants born to ZIKV-infected mothers. To reach the fetus the 
      virus must overcome the defense mechanisms provided by trophoblast cells. 
      Additionally, in the first trimester, the integrity of the placenta is critical 
      for fetal protection as damage to differentiating trophoblast can affect 
      placental formation and function. We sought to investigate the effect of ZIKV 
      infection on trophoblast cells and the factors that might increase the risk for 
      ZIKV infection during pregnancy. METHODS: First-trimester human trophoblast 
      cells, Swan 7.1, were infected with ZIKV, herpes simplex virus-2 (HSV-2), and 
      yellow fiver (YFV). C57BL/6 pregnant mice were infected with HSV-2, ZIKV, or 
      coinfection. Placental viral titers were determined by RT-PCR. RESULTS: ZIKV 
      infection induces apoptosis in first-trimester trophoblasts and prevents 
      differentiation of these cells. Furthermore, HSV-2 infection enhances placental 
      sensitivity to ZIKV by enhancing the expression of TAM receptors, which 
      facilitate ZIKV cell entry. CONCLUSION: These findings may explain the mechanism 
      by which ZIKV breaches the placental barrier to access the fetus. Furthermore, 
      our results suggest that patients with HSV-2 infection are at a higher risk for 
      the teratogenic effects induced by ZIKV.
CI  - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Aldo, Paulomi
AU  - Aldo P
AD  - Division of Reproductive Sciences, Department of Obstetrics, Gynecology and 
      Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
FAU - You, Yuan
AU  - You Y
AD  - Division of Reproductive Sciences, Department of Obstetrics, Gynecology and 
      Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
FAU - Szigeti, Klara
AU  - Szigeti K
AD  - Department of Comparative Medicine, Yale University School of Medicine, New 
      Haven, CT, USA.
FAU - Horvath, Tamas L
AU  - Horvath TL
AD  - Division of Reproductive Sciences, Department of Obstetrics, Gynecology and 
      Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
AD  - Department of Comparative Medicine, Yale University School of Medicine, New 
      Haven, CT, USA.
FAU - Lindenbach, Brett
AU  - Lindenbach B
AD  - Department of Microbial Pathogenesis, Yale University School of Medicine, New 
      Haven, CT, USA.
FAU - Mor, Gil
AU  - Mor G
AD  - Division of Reproductive Sciences, Department of Obstetrics, Gynecology and 
      Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. 
      gil.mor@yale.edu.
LA  - eng
SI  - GENBANK/FSS13025
GR  - R56 AI124356/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160910
PL  - Denmark
TA  - Am J Reprod Immunol
JT  - American journal of reproductive immunology (New York, N.Y. : 1989)
JID - 8912860
SB  - IM
CIN - Am J Reprod Immunol. 2017 Feb;77(2):null. PMID: 27868270
CIN - Am J Reprod Immunol. 2017 Feb;77(2):null. PMID: 28028879
MH  - Apoptosis
MH  - Cell Line
MH  - Coinfection
MH  - Female
MH  - Fetus
MH  - Herpes Genitalis/*immunology
MH  - Herpesvirus 2, Human/*immunology
MH  - Humans
MH  - Infant, Newborn
MH  - Infant, Newborn, Diseases/*epidemiology
MH  - Infectious Disease Transmission, Vertical
MH  - Microcephaly/*epidemiology
MH  - Placenta/*physiology
MH  - Pregnancy
MH  - Pregnancy Complications, Infectious/*immunology
MH  - Trophoblasts/*immunology/pathology/virology
MH  - Zika Virus/*immunology
MH  - Zika Virus Infection/*epidemiology/*immunology
OTO - NOTNLM
OT  - HSV-1/2
OT  - co-infection
OT  - fetal viral infection
OT  - pika virus
OT  - placenta
OT  - pregnancy
EDAT- 2016/09/11 06:00
MHDA- 2017/12/27 06:00
CRDT- 2016/09/11 06:00
PHST- 2016/08/16 00:00 [received]
PHST- 2016/08/23 00:00 [accepted]
PHST- 2016/09/11 06:00 [pubmed]
PHST- 2017/12/27 06:00 [medline]
PHST- 2016/09/11 06:00 [entrez]
AID - 10.1111/aji.12578 [doi]
PST - ppublish
SO  - Am J Reprod Immunol. 2016 Nov;76(5):348-357. doi: 10.1111/aji.12578. Epub 2016 
      Sep 10.