Zika Virus Infection in Hypothalamus Causes Hormone Deficiencies and Leads to Irreversible Growth Delay and Memory Impairment in Mice

Abstract

Summary: Zika virus (ZIKV) can cause microcephaly in the fetus. However, its effects on body growth and the development of children with postnatal ZIKV infection are largely unknown. To examine this, we intraperitoneally challenged mouse pups with ZIKV. Infection causes an irreversible growth delay and deficits in spatial learning and memory, with growth-relevant hormones significantly reduced during infection. These effects are associated with ZIKV RNA expression in the hypothalamus, blood, and brain but not in the pituitary and thyroid. Infection is also associated with hypothalamic inflammation, and ZIKV antigen is detectable in neuroendocrine cells producing thyrotropin-releasing hormone. Moreover, early administration of growth hormone could significantly improve growth delay. Our results demonstrate that ZIKV can infect the hypothalamus, causing multi-hormone deficiencies and delayed growth and development in a mouse model. Therefore, prospective multidisciplinary follow-up of ZIKV-infected children may be necessary to understand potential effects of this virus on childhood development. : Wu et al. find that ZIKV infection in mouse pups causes hypothalamic damage and dysfunction of the hypothalamic-pituitary axis, featuring multi-hormone deficiencies and resulting in irreversible growth delay and memory impairment during adulthood. Early administration of the relevant hormones could partially improve the long-term sequelae in the neuroendocrine system. Keywords: Zika virus, hypothalamus, multi-hormone deficiencies, growth delay, memory impairment, TSH-producing endocrine cells