Abstract

Tacaribe virus (TCRV) is a mammalian arenavirus that was first isolated from artibeus bats in the 1950s. Subsequent experimental infection of Jamaican fruit bats (Artibeus jamaicensis) caused a disease similar to that of naturally infected bats. Although substantial attention has focused on bats as reservoir hosts of viruses that cause human disease, little is known about the interactions between bats and their pathogens. We performed a transcriptome-wide study to illuminate the response of Jamaican fruit bats experimentally infected with TCRV. Differential gene expression analysis of multiple tissues revealed global and organ-specific responses associated with innate antiviral responses, including interferon alpha/beta and Toll-like receptor signaling, activation of complement cascades, and cytokine signaling, among others. Genes encoding proteins involved in adaptive immune responses, such as gamma interferon signaling and costimulation of T cells by the CD28 family, were also altered in response to TCRV infection. Immunoglobulin gene expression was also elevated in the spleens of infected bats, including IgG, IgA, and IgE isotypes. These results indicate an active innate and adaptive immune response to TCRV infection occurred but did not prevent fatal disease. This de novo assembly provides a high-throughput data set of the Jamaican fruit bat and its host response to TCRV infection, which remains a valuable tool to understand the molecular signatures involved in antiviral responses in bats. IMPORTANCE As reservoir hosts of viruses associated with human disease, little is known about the interactions between bats and viruses. Using Jamaican fruit bats infected with Tacaribe virus (TCRV) as a model, we characterized the gene expression responses to infection in different tissues and identified pathways involved with the response to infection. This report is the most detailed gene discovery work in the species to date and the first to describe immune gene expression responses in bats during a pathogenic viral infection.

Highlights

  • Tacaribe virus (TCRV) is a mammalian arenavirus that was first isolated from artibeus bats in the 1950s

  • Using Jamaican fruit bats infected with Tacaribe virus (TCRV) as a model, we characterized the gene expression responses to infection in different tissues and identified pathways involved with the response to infection

  • We previously reported a high mortality rate in Jamaican fruit bats experimentally infected with TCRV, in which high-dose inoculations (106 50% tissue culture infective doses [TCID50]) caused significant and fatal disease as early as 10 days postinfection [22]

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Summary

Introduction

Tacaribe virus (TCRV) is a mammalian arenavirus that was first isolated from artibeus bats in the 1950s. Certain bat species have been identified as reservoir hosts of zoonotic viruses associated with significant human morbidity and mortality, including rabies virus and other lyssaviruses, Marburg virus, Nipah virus, and Hendra virus [3] They are suspected reservoirs of other viruses, such as the ebolaviruses, and Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses (CoVs) [4,5,6]. Because bats are important members of their ecosystems, a better understanding of the immune responses and subsequent pathogenesis to infectious agents is essential To this end, we developed a laboratory model for the study of infection of Jamaican fruit bats (Artibeus jamaicensis) by a natural bat pathogen, Tacaribe virus (TCRV) [11, 21, 22]

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