Adaptive Immune Responses to Zika Virus Are Important for Controlling Virus Infection and Preventing Infection in Brain and Testes.
The recent association between Zika virus (ZIKV) and neurologic complications, including Guillain-Barré syndrome in adults and CNS abnormalities in fetuses, highlights the importance in understanding the immunological mechanisms controlling this emerging infection. Studies have indicated that ZIKV evades the human type I IFN response, suggesting a role for the adaptive immune response in resolving infection. However, the inability of ZIKV to antagonize the mouse IFN response renders the virus highly susceptible to circulating IFN in murine models. Thus, as we show in this article, although wild-type C57BL/6 mice mount cell-mediated and humoral adaptive immune responses to ZIKV, these responses were not required to prevent disease. However, when the type I IFN response of mice was suppressed, then the adaptive immune responses became critical. For example, when type I IFN signaling was blocked by Abs inRag1-/-mice, the mice showed dramatic weight loss and ZIKV infection in the brain and testes. This phenotype was not observed in Ig-treatedRag1-/-mice or wild-type mice treated with anti-type I IFNR alone. Furthermore, we found that the CD8+T cell responses of pregnant mice to ZIKV infection were diminished compared with nonpregnant mice. It is possible that diminished cell-mediated immunity during pregnancy could increase virus spread to the fetus. These results demonstrate an important role for the adaptive immune response in the control of ZIKV infection and imply that vaccination may prevent ZIKV-related disease, particularly when the type I IFN response is suppressed as it is in humans.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Clayton W
CW
Winkler
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Lara M
0000-0003-0221-9770
LM
Myers
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Tyson A
TA
Woods
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Ronald J
0000-0002-6932-2337
RJ
Messer
Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Aaron B
0000-0003-4772-763X
AB
Carmody
Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; and.
Kristin L
KL
McNally
Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Dana P
DP
Scott
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Kim J
0000-0001-8523-4911
KJ
Hasenkrug
Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; and.
Sonja M
SM
Best
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; petersonka@niaid.nih.gov.
Karin E
0000-0003-4177-7249
KE
Peterson
D056704:Adaptive Immunity; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001921:Brain / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D057131:Immune Evasion; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy / Q000276:immunology; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D013737:Testis / Q000276:immunology / Q000821:virology*; D000071244:Zika Virus / Q000276:immunology*; D000071243:Zika Virus Infection / Q000453:epidemiology / Q000276:immunology*
D019138:Antibodies, Blocking; D018398:Homeodomain Proteins; D007370:Interferon Type I; C064658:RAG-1 protein