Zika virus shedding in the stool and infection through the anorectal mucosa in mice.

Chunfeng Li, Yong-Qiang Deng, Shulong Zu, Natalie Quanquin, Jingzhe Shang, Min Tian, Xue Ji, Na-Na Zhang, Hao-Long Dong, Yan-Peng Xu, Ling-Zhai Zhao, Fu-Chun Zhang, Xiao-Feng Li, Aiping Wu, Genhong Cheng, Cheng-Feng Qin
Author Information
  1. Chunfeng Li: Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
  2. Yong-Qiang Deng: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  3. Shulong Zu: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  4. Natalie Quanquin: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
  5. Jingzhe Shang: Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
  6. Min Tian: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  7. Xue Ji: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  8. Na-Na Zhang: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  9. Hao-Long Dong: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  10. Yan-Peng Xu: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  11. Ling-Zhai Zhao: Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China.
  12. Fu-Chun Zhang: Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China.
  13. Xiao-Feng Li: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  14. Aiping Wu: Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
  15. Genhong Cheng: Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China. gcheng@mednet.ucla.edu.
  16. Cheng-Feng Qin: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. qincf@bmi.ac.cn.

Abstract

Zika virus (ZIKV) has elicited global concern due to its unique biological features, unusual transmission routes, and unexpected clinical outcomes. Although ZIKV transmission through anal intercourse has been reported in humans, it remains unclear if ZIKV is detectable in the stool, if it can infect the host through the anal canal mucosa, and what the pathogenesis of such a route of infection might be in the mouse model. Herein, we demonstrate that ZIKV RNA can be recovered from stools in multiple mouse models, as well as from the stool of a ZIKV patient. Remarkably, intra-anal (i.a.) inoculation with ZIKV leads to efficient infection in both Ifnar1 and immunocompetent mice, characterized by extensive viral replication in the blood and multiple organs, including the brain, small intestine, testes, and rectum, as well as robust humoral and innate immune responses. Moreover, i.a. inoculation of ZIKV in pregnant mice resulted in transplacental infection and delayed fetal development. Overall, our results identify the anorectal mucosa as a potential site of ZIKV infection in mice, reveal the associated pathogenesis of i.a. infection, and highlight the complexity of ZIKV transmission through anal intercourse.

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Grants

  1. R01 AI069120/NIAID NIH HHS
  2. R01 AI140718/NIAID NIH HHS
  3. R01 AI056154/NIAID NIH HHS
  4. R56 AI078389/NIAID NIH HHS
  5. R01 AI078389/NIAID NIH HHS

MeSH Term

Animals
Feces
Female
Humans
Immunity, Innate
Intestinal Mucosa
Male
Mice
Mice, Inbred C57BL
Pregnancy
Pregnancy Complications
Rectum
Virus Replication
Virus Shedding
Zika Virus
Zika Virus Infection