Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; University of Chinese Academy of Sciences, Beijing 100091, China.
Clin Microbiol Infect. 2021 Mar;27(3):469.e1-469.e7. doi: 10.1016/j.cmi.2020.04.021. Epub 2020 Apr 25.
Infectious Zika viral particles were detected in human milk; however, whether they can be transmitted via breastfeeding remains unknown, so our objective was to clarify this.
Here, in a natural breastfeeding model, wild-type (C57Bl/6; WT) or interferon α/β (IFNα/β) receptor-deficient (A129; KO) murine dams on day 1 post-delivery were infected with Zika virus (ZIKV) intraperitoneally, and the neonates were suckled. In a novel artificial feeding model, WT suckling mice at 1 day old were fed with ZIKV alone or ZIKV and human breast milk mixtures. Thereafter, the virus distribution, clinical progression and neuropathology in the WT or KO neonates were characterized to evaluate the risk of ZIKV transmission through breast milk.
In natural breastfeeding, viral RNAs (8/8) and infectious viral particles (7/8) were extensively present in the mammary glands of KO dams. All tested KO neonates (5/5), and none of WT neonates (0/9), were infected with ZIKV. In artificial feeding, 100% of the WT neonates (two groups, 12/12 and 16/16) were infected and developed some signs of neurodegeneration. ZIKV tended to seed and accumulate in the lungs and were subsequently disseminated to other tissues in both 16 naturally suckled and 19 artificially fed infected neonates. As human breast milk was mixed with ZIKV and fed to WT neonates, 45% individuals (9/20) were infected; in the infected neonates, the viral spread to the brain was delayed, and the clinical outcomes were alleviated.
These results demonstrated that suckling mice can be infected with ZIKV through suckling, and breast milk has potential antiviral activity, inhibiting ZIKV infection.
已在人乳中检测到感染性寨卡病毒颗粒;然而,其是否可通过母乳喂养传播仍不清楚,因此我们的目的是阐明这一点。
在此,在自然母乳喂养模型中,产后第 1 天的野生型(C57Bl/6;WT)或干扰素 α/β(IFNα/β)受体缺陷(A129;KO)母鼠经腹腔内感染寨卡病毒(ZIKV),并让新生鼠进行哺乳。在新的人工喂养模型中,1 日龄 WT 哺乳鼠单独或与 ZIKV 和人乳混合物一起喂养 ZIKV。此后,对 WT 或 KO 新生鼠的病毒分布、临床进展和神经病理学进行了特征分析,以评估 ZIKV 通过母乳传播的风险。
在自然母乳喂养中,KO 母鼠的乳腺中广泛存在病毒 RNA(8/8)和感染性病毒颗粒(7/8)。所有检测到的 KO 新生鼠(5/5)均未感染 ZIKV,而 WT 新生鼠(0/9)均未感染 ZIKV。在人工喂养中,100%的 WT 新生鼠(两组,12/12 和 16/16)均被感染并出现一些神经退行性病变迹象。ZIKV 倾向于在肺部定植和积累,随后在 16 只自然哺乳和 19 只人工喂养感染的新生鼠中传播到其他组织。当人乳与 ZIKV 混合并喂养给 WT 新生鼠时,45%的个体(9/20)被感染;在感染的新生鼠中,病毒向大脑的传播被延迟,临床结局得到缓解。
这些结果表明,通过哺乳,新生鼠可感染 ZIKV,并且母乳具有潜在的抗病毒活性,可抑制 ZIKV 感染。