Abstract
Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide and causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy. Protection against EHV-1 disease is elusive due to establishment of latency and immune-modulatory features of the virus. These include the modulation of interferons, cytokines, chemokines, antigen presentation, and cellular immunity. Because the modulation of immunity likely occurs at the site of first infection—the respiratory epithelium, we hypothesized that the mucosal influenza vaccine Flu Avert® I.N. (Flu Avert), which is known to stimulate strong antiviral responses, will enhance antiviral innate immunity, and that these responses would also provide protection from EHV-1 infection. To test our hypothesis, primary equine respiratory epithelial cells (ERECs) were treated with Flu Avert, and innate immunity was evaluated for 10 days following treatment. The timing of Flu Avert treatment was also evaluated for optimal effectiveness to reduce EHV-1 replication by modulating early immune responses to EHV-1. The induction of interferons, cytokine and chemokine mRNA expression, and protein secretion was evaluated by high-throughput qPCR and multiplex protein analysis. Intracellular and extracellular EHV-1 titers were determined by qPCR. Flu Avert treatment resulted in the modulation of IL-8, CCL2, and CXCL9 starting at days 5 and 6 post-treatment. Coinciding with the timing of optimal chemokine induction, our data also suggested the same timing for reduction of EHV-1 replication. In combination, our results suggest that Flu Avert may be effective at counteracting some of the immune-modulatory properties of EHV-1 at the airway epithelium and the peak for this response occurs 5–8 days post-Flu Avert treatment. Future in vivo studies are needed to investigate Flu Avert as a prophylactic in situations where EHV-1 exposure may occur.
Highlights
Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide
Our hypothesis was that treatment of equine respiratory epithelial cells (ERECs) to a live-attenuated influenza vaccine (LAIV) would stimulate innate immunity, and that this response would protect cells against EHV-1 infection and replication
While it has been well-established in humans that influenza virus infection or LAIV vaccination stimulates mucosal immunity, very little work has been done evaluating the equine respiratory epithelial innate immune response to equine influenza virus (EIV) or equine LAIV
Summary
Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide. It is responsible for causing respiratory disease, late term abortion in pregnant mares, or the crippling neurologic disease equine herpesvirus myeloencephalopathy (EHM). Virus neutralizing (VN) antibodies can be detected in the serum and nasal mucosa and are associated with protection against clinical respiratory disease and nasal shedding upon re-exposure to the virus [9,10,11,12]. High serum antibody levels following vaccination or infection do not correlate with protection from viremia or subsequent secondary disease manifestations, such as abortion or EHM [4, 9, 13]. High levels of cytotoxic lymphocyte (CTL) precursor frequencies are thought to be crucial for protection from viremia, abortion, and EHM [9, 12, 13]
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