First Published Study with Embryonated Hen Egg Infected with Zika Virus Is Dated from 1952

The study entitled “Zika Virus Induced Mortality and Microcephaly in Chicken Embryos” has presented new and important information about Zika virus (ZIKV) infection in chicken embryonic eggs [1]. Although there was a peak in the publications related to ZIKV between 2015 and 2016, it is important to reassure that ZIKV was discovered in 1947 [2], and interesting studies were developed almost 60 years ago, including the first experiments with animal models. Most of the research with ZIKV in that time also included other flaviviruses, especially yellow fever virus, which means the word ZIKV might not be found in the title of the article even if they have studied ZIKV. One important article published in 1952 by Taylor used chicken embryonic eggs [3], which is missing in the previously cited publication from 2016. Antique studies are hard to be tracked down, but at the same time it is important to mention this study because it was the first to develop this model for ZIKV infection. Taylor (1952) showed that ZIKV was able to infect chick embryos using an African viral strain, MR766, isolated from an infected monkey. The infection persisted up to 9 days postinfection (dpi) through yolk, amniotic sac, and allantoic sac injection. The initial period to detect ZIKV differed according to the site of injection, 2 dpi for yolk and amniotic sac and 4 dpi for allantoic sac injections. There was no significant difference between the titers detected in body and brain of the embryo. In addition, ZIKV infection was not fatal [3]. Interestingly, Goodfellow et al. (2016) study used a ZIKV Mexican strain, named Mex 1–44, and isolated from Aedes aegypti mosquitoes in Chiapas, Mexico, and described lethality in high doses of the virus. The virus was detected in many organs, and a microcephaly-like phenotype was described as a result of the impairment caused in the central nervous system by ZIKV [1,4]. It is important to highlight that both studies have used different strains, and actually this is one interesting point, because the strain MR766 used in the study of 1952 had been passaged hundreds of times in mouse brain, whereas Mex 1–44, used in the 2016 study, was recently isolated. It is still unknown how the multiple passages of the virus in the mouse brain could interfere with ZIKV pathogenesis; however, it is important to note that the recent isolated strains have been associated with neurological problems, especially in South and Central America. Both articles are unique and have an important contribution to better understand ZIKV biology and the development of the diseases associated with the infection. It is interesting to be able to connect studies so distant by time but with the same exciting investigation about ZIKV infection and replication.