Time: a key factor defining Zika-dengue interactions
When Zika virus circulation was detected in French Polynesia in 2013 and then in Latin America by 2015, most of the investigators in the field thought that this would be another rash and fever causing flavivirus. We all were wrong.
By Carlos A. Sariol and Daniela Weiskopf
The reports of an increase of Guillain barre syndrome, microcephaly and other congenital malformations associated with Zika infection confirmed the weird behavior of this virus compared with its closely related relatives belonging to the same family. The situation was such alarming that the WHO called for an Emergency of International Concern on February 1st, 2016. On top of that, we face the fact that Zika spread occurs in areas where its cousin, dengue virus is endemic. Evidence supports the fact that sequential infections with different dengue serotypes may result in worse clinical presentations know as severe dengue. The mortality rate of severe dengue is above 80%. It would be the same case for dengue-Zika or Zika-dengue sequential infections? Would previous dengue immunity increase the pathogenesis of Zika virus or vice versa? This is and will continue to be for a while a hot debate in the field. In previous work from our group, we suggested, for the first time, that the presence of dengue immunity may not increase Zika pathogenesis. Furthermore, our experimental results suggested that at least 3 years of previous dengue exposure may even curb Zika replication and potentially its symptoms. After a few years of Zika circulation (2014-2018) causing a huge but transient epidemic, dengue was displaced and almost disappear until its reemergence early 2019 in some Caribbean and Latin American countries. In the recent work we explore the potential impact of a different interval of time between Zika and dengue infection in the pathogenesis of dengue.Our results provided experimental answers to the dengue displacement in the human population. We showed that exposing non-human primates to dengue two months or ten months after being infected with Zika did not increase dengue replication or worse clinical or laboratory and inflammatory parameters. Moreover, our results showed that about one year of Zika immunity was linked to a better dengue viremic control and an improved magnitude of the cellular immune response. Our results are indeed being tested in a real setting. Currently, there is an ongoing dengue epidemic in different Latin American and Caribbean countries where a previous Zika epidemic took place. An important angle of our findings is that those support the implementation of Zika vaccines in dengue-endemic areas. Our result showed that dengue infection in individuals with about one year of Zika immunity, the humoral and cellular immune response against subsequent heterologous dengue infections was, in fact, improved. Prospective clinical and epidemiological data from the current and future dengue epidemics, occurring at a longer period of times after the Zika epidemic, will help to expand our understanding of the complex interactions among flaviviruses.