Abstract
The recent emergence and rapid geographic expansion of Zika virus (ZIKV) poses a significant challenge for public health. Although historically causing only mild febrile illness, recent ZIKV outbreaks have been associated with more severe neurological complications, such as Guillain-Barré syndrome and fetal microcephaly. Here we demonstrate that two contemporary (2015) ZIKV isolates from Puerto Rico and Brazil may have increased replicative fitness in human astrocytoma cells. Over a single infectious cycle, the Brazilian isolate replicates to higher titers and induces more severe cytopathic effects in human astrocytoma cells than the historical African reference strain or an early Asian lineage isolate. In addition, both contemporary isolates induce significantly more double-stranded RNA in infected astrocytoma cells, despite similar numbers of infected cells across isolates. Moreover, when we quantified positive- and negative-strand viral RNA, we found that the Asian lineage isolates displayed substantially more negative-strand replicative intermediates than the African lineage isolate in human astrocytoma cells. However, over multiple rounds of infection, the contemporary ZIKV isolates appear to be impaired in cell spread, infecting a lower proportion of cells at a low MOI despite replicating to similar or higher titers. Taken together, our data suggests that contemporary ZIKV isolates may have evolved mechanisms that allow them to replicate with increased efficiency in certain cell types, thereby highlighting the importance of cell-intrinsic factors in studies of viral replicative fitness.
Highlights
The recent emergence and rapid geographic expansion of the mosquito-borne Zika Virus (ZIKV)poses a significant burden on the global health infrastructure [1]
The clinical manifestations of ZIKV infection during the Yap Island epidemic were relatively similar to historical descriptions; resulting in mild, self-limiting, febrile illness characterized by rash, arthralgia, conjunctivitis, and headaches [3,5]
Phylogenetic analyses demonstrate that ZIKV can be divided into two main lineages: African and
Summary
The recent emergence and rapid geographic expansion of the mosquito-borne Zika Virus (ZIKV). A recent investigation uncovered a single nucleotide substitution in the prM region of the viral polyprotein that increases ZIKV infectivity in human and mouse neural progenitor cells and leads to significant fetal microcephaly in mice, resulting in greater mortality of neonatal mice [18]. Another polymorphism found in the NS1 region of contemporary ZIKV isolates results in increased NS1 antigenemia in mice, enhanced infectivity in Aedes mosquitoes, and reduced induction of antiviral signaling in human cells [19,20]. Our results suggest that the contemporary ZIKV isolates may have evolved mechanisms that allow them to replicate with increased efficiency in certain cell types and highlight the importance of cell-intrinsic factors in studies of viral replicative fitness
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