Zika Virus and Microcephaly Aagaard KM, Lahon A, Suter MA, Arya RP, Seferovic MD, Vogt MB, Hu M, Stossi F, Mancini MA, Harris RA, et al. 2017. Primary human placental trophoblasts are permissive for Zika virus (ZIKV) replication. Sci Rep 7: 41389 A warmer climate and changing rainfall patterns may also create hospitable environments for mosquitoes, ticks and other climate sensitive vectors that spread such diseases as malaria, chikungunya, dengue fever and the zika virus. Compared with other flaviviruses, one striking feature of the current zika virus (ZIKV) epidemic is the association of viral infection with a marked increase of risk for congenital microcephaly and serious neurologic complications (Petersen et al. 2016), which triggered widespread efforts to understand the molecular basis of infection. Similar to its close relatives in the Flaviviridae family, such as DENV, yellow fever, Japanese encephalitis, and West Nile viruses (WNV), ZIKV has an icosahedral outer envelope and a dense inner core containing one single-strand positive sense RNA genome between 10,000 and 11,000 base pairs in length (Chambers et al. 1990; Kuno and Chang 2007). The genome of ZIKV encodes a single polyprotein that is post-translationally cleaved by host and viral proteases into three structural proteins (capsid [C], premembrane [prM], and envelope [E]) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) Microcephaly is a neurodevelopmental disorder, which is characterized by a marked reduction in brain size and intellectual disability caused by impaired cell proliferation and the death of cortical progenitor cells and their neuronal progeny (Barbelanne and Tsang 2014). Through January 26 of 2016, 10,441 suspected and 2366 confirmed ZIKV-associated microcephaly cases have been reported in Brazil (Zika-Epidemiological Report by the Pan-American Health Organization [PAHO] and World Health Organization [WHO]), the country that has experienced the highest ZIKV infection rates worldwide. The increase of microcephaly cases and the coincidental ZIKV outbreak led the WHO to declare a Public Health Emergency of International Concern in early 2016 (Heymann et al. 2016). This ignited tremendous interest and immediate efforts by scientists to understand the impact of ZIKV on human brain development and the mechanistic link between ZIKV infection and microcephaly. In the past year, rapid and stunning progress has been made toward developing stem cell-based cellular models, primary human tissues, and animal models to understand its pathogenesis, investigate underlying mechanisms, and develop therapeutics (Abbink et al. 2016; Cugola et al. 2016; Dudley et al. 2016; Garcez et al. 2016; Lazear et al. 2016; Li et al. 2016a,b; Miner et al. 2016a; Ming et al. 2016; Qian et al. 2016, 2017; Rossi et al. 2016; Tang et al. 2016; Wu et al. 2016; Xu et al. 2016; Hirsch et al. 2017).