Zika virus (ZIKV) infections cause a mild febrile illness characterized by headache, myalgia, fever, rash and non-purulent conjunctivitis. Recently, in the Brazilian ZIKV outbreak, more than 200,000 people were notified with the disease and some complications associated with this infection were identified. Due to the rapid spread of the disease over Central and South America, the aim of this project is to determine differences in infection between an African strain (prototype MR766) and the strain circulating in Brazil (Asian lineage ZikaSPH2015). Analysis of nucleotide and protein sequences of both strains was carried out in silico, by comparing their sequences and performing the prediction of the envelope protein structure. Comparative infection with both strains was performed in vitro using Aedes cell lines and although similar effects were observed in cell lineages, the ZikaSPH2015 strain had a better viral fitness in Aedes aegypti cells than in Ae. albopictus. Analysis of codon usage showed an increased usage of some codons in Ae. aegypti and ZikaSPH2015. Immune response evaluation showed fully heterologous protective antibodies, but cytokine gene expression demonstrated that MR766 induces a more intense immune response than ZikaSPH2015. The results presented here indicate that ZIKV Asian strain replicates more efficiently in Aedes aegypti cells, which may explain the higher intensity and distribution of this lineage outbreaks over the African strain ones. In addition, the Asian lineage might have a mechanism that interferes with antiviral response allowing for a prolonged viremia in some individuals leading to the severe clinical implications related to this infection.