Comparative susceptibility of Old World and New World bat cell lines to Zika virus: Insights into viral replication and inflammatory responses

Background: The emergence of flaviviruses and other arboviruses in novel geographic locations, arthropod vectors, and vertebrate amplification hosts complicates control and eradication efforts. Many flaviviruses continue to impact global health, including Zika virus (ZIKV) which has expanded to a global health threat, yet many questions remain surrounding its ecology and inter-epidemic maintenance. While bats are known to harbor several medically important viruses without clinical disease, their role in the sylvatic transmission cycle of arboviruses remains unresolved. Reports describing the susceptibility of different bat species to infection with ZIKV are inconsistent, and the immunological mechanisms underpinning this variability have not been well-characterized. Methodology/Principal Findings: We compared the permissiveness and immune responses of cell lines derived from two frugivorous bat species: the Egyptian fruit bat (Rousettus aegyptiacus) and Jamaican fruit bat (Artibeus jamaicensis). Using multi-step growth curves, we compared infection dynamics of two genetically distinct ZIKV strains, African lineage (ZIKV/MR766) and Asian-American lineage (ZIKV/PRVABC59) and compared transcriptomic responses to both lineages in susceptible bat-derived cell lines. Conclusions/Significance: Our results highlight species-specific differences in ZIKV susceptibility across bat-derived cell lines, with both ZIKV strains replicating to high titers on R. aegyptiacus cells but not on A. jamaicensis cells. We detected pro-inflammatory transcriptomic signatures in R. aegyptiacus cells infected with both ZIKV lineages. Notably, both the Asian-American and African ZIKV lineages demonstrated some capacity for immune evasion and productive replication in the R. aegyptiacus cell line. Author summary: This study investigates how different lineages of Zika virus (ZIKV) interact with bat cells, specifically examining the cellular inflammatory and antiviral responses. We compare host-virus interactions using cell lines derived from two frugivorous bat species (Rousettus aegyptiacus and Artibeus jamaicensis). Our results highlight differences in cellular permissiveness and spur additional questions surrounding how infection outcomes are shaped by host taxonomy, viral lineage, and host-virus interactions at the cellular level. Surprisingly, cells derived from R. aegyptiacus, the reservoir host of Marburg virus, revealed pro-inflammatory transcriptomic signatures that reflect what is seen during acute infection of humans and non-human primates. African lineage ZIKV (MR766) caused a more robust immune response than Asian-American lineage ZIKV (PRVABC59). In contrast, our A. jamaicensis-derived cells appeared resistant to infection with both ZIKV lineages. Our data highlight the importance of comparing host-virus interactions across possible host species and suggest that events occurring after viral entry may shape infection outcomes.