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TAM Receptors Are Not Required for Zika Virus Infection in Mice.

Abstract Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl(-/-), Mertk(-/-), Axl(-/-)Mertk(-/-), and Axl(-/-)Tyro3(-/-) mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection.
PMID
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Authors

Mayor MeshTerms
Keywords

CNS

congenital infection

flavivirus

neurotropic virus

pregnancy

viral entry

Journal Title cell reports
Publication Year Start




PMID- 28423319
OWN - NLM
STAT- In-Process
DA  - 20170419
LR  - 20170419
IS  - 2211-1247 (Electronic)
VI  - 19
IP  - 3
DP  - 2017 Apr 18
TI  - TAM Receptors Are Not Required for Zika Virus Infection in Mice.
PG  - 558-568
LID - S2211-1247(17)30419-9 [pii]
LID - 10.1016/j.celrep.2017.03.058 [doi]
AB  - Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection
      with the Zika virus (ZIKV), an emerging flavivirus of global public health
      concern. To investigate the requirement of TAM receptors for ZIKV infection, we
      used several routes of viral inoculation and compared viral replication in
      wild-type versus Axl-/-, Mertk-/-, Axl-/-Mertk-/-, and Axl-/-Tyro3-/- mice in
      various organs. Pregnant and non-pregnant mice treated with
      interferon-alpha-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected
      subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence
      of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV
      showed no difference in mucosal viral titers. Similarly, in young mice that were 
      infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred
      in the absence of TAM receptors, and no differences in cell tropism were
      observed. These findings indicate that, in mice, TAM receptors are not required
      for ZIKV entry and infection.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Hastings, Andrew K
AU  - Hastings AK
AD  - Section of Infectious Diseases, Department of Internal Medicine, Yale University 
      School of Medicine, New Haven, CT 06520, USA.
FAU - Yockey, Laura J
AU  - Yockey LJ
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT
      06520, USA.
FAU - Jagger, Brett W
AU  - Jagger BW
AD  - Division of Infectious Diseases, Department of Medicine, Washington University
      School of Medicine, Saint Louis, MO 63110, USA.
FAU - Hwang, Jesse
AU  - Hwang J
AD  - Section of Infectious Diseases, Department of Internal Medicine, Yale University 
      School of Medicine, New Haven, CT 06520, USA.
FAU - Uraki, Ryuta
AU  - Uraki R
AD  - Section of Infectious Diseases, Department of Internal Medicine, Yale University 
      School of Medicine, New Haven, CT 06520, USA.
FAU - Gaitsch, Hallie F
AU  - Gaitsch HF
AD  - Section of Infectious Diseases, Department of Internal Medicine, Yale University 
      School of Medicine, New Haven, CT 06520, USA.
FAU - Parnell, Lindsay A
AU  - Parnell LA
AD  - Department of Obstetrics and Gynecology, Washington University School of
      Medicine, Saint Louis, MO 63110, USA.
FAU - Cao, Bin
AU  - Cao B
AD  - Department of Obstetrics and Gynecology, Washington University School of
      Medicine, Saint Louis, MO 63110, USA.
FAU - Mysorekar, Indira U
AU  - Mysorekar IU
AD  - Department of Obstetrics and Gynecology, Washington University School of
      Medicine, Saint Louis, MO 63110, USA; Department of Pathology and Immunology,
      Washington University School of Medicine, Saint Louis, MO 63110, USA.
FAU - Rothlin, Carla V
AU  - Rothlin CV
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT
      06520, USA.
FAU - Fikrig, Erol
AU  - Fikrig E
AD  - Section of Infectious Diseases, Department of Internal Medicine, Yale University 
      School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute,
      Chevy Chase, MD 20815, USA. Electronic address: [email protected]
FAU - Diamond, Michael S
AU  - Diamond MS
AD  - Division of Infectious Diseases, Department of Medicine, Washington University
      School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular
      Microbiology, Washington University School of Medicine, Saint Louis, MO 63110,
      USA; Department of Obstetrics and Gynecology, Washington University School of
      Medicine, Saint Louis, MO 63110, USA; Department of Pathology and Immunology,
      Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic 
      address: [email protected]
FAU - Iwasaki, Akiko
AU  - Iwasaki A
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT
      06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
      Electronic address: [email protected]
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
OTO - NOTNLM
OT  - CNS
OT  - congenital infection
OT  - flavivirus
OT  - neurotropic virus
OT  - pregnancy
OT  - viral entry
EDAT- 2017/04/20 06:00
MHDA- 2017/04/20 06:00
CRDT- 2017/04/20 06:00
PHST- 2017/02/12 [received]
PHST- 2017/03/16 [revised]
PHST- 2017/03/20 [accepted]
AID - S2211-1247(17)30419-9 [pii]
AID - 10.1016/j.celrep.2017.03.058 [doi]
PST - ppublish
SO  - Cell Rep. 2017 Apr 18;19(3):558-568. doi: 10.1016/j.celrep.2017.03.058.

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