Nasal Immunity and it's Function in Preventing Transmission of EHV-1 in Immune Horses

Principal Investigator: Bettina Wagner

Department of Population Medicine and Diagnostic Sciences
Sponsor: Harry M. Zweig Memorial Fund for Equine Research
Title: Nasal Immunity and it's Function in Preventing Transmission of EHV-1 in Immune Horses
Project Amount: $71,571
Project Period: January 2020 to December 2020

DESCRIPTION (provided by applicant): 

Equine herpesvirus type 1 (EHV-1) continues to cause outbreaks including those of equine herpesvirus myeloencephalopathy (EHM), a severe neurologic disease. This year alone, several EHM cases were reported in New York State (NYS) leading to 3-4 weeks of quarantine at four different barns/stables. EHM outbreaks and quarantine have a serious impact on equine health, restrict horse transport, racing and competitions, and economically affect equine businesses, horse owners, and the equine industry. Currently, all horses at a quarantined location are kept there for the same time for general precaution and preventing the spread EHV-1 to other horses. However, these decisions are made without consideration of immunity. Typically, only a few horses at the quarantined facility are getting sick while several horses appear completely healthy and unaffected by the virus. Is it appropriate to release healthy horses earlier from quarantine and how can we make an informed decision on an early release without risking further spread of the disease? Our recent research findings indicate that immune horses that are immune against EHV-1 do not show clinical signs after infection with high doses of neuropathogenic EHV-1. In addition, immune horses neither shed any infectious virus when tested 24 hours post infection or later, nor do they develop cell-associated viremia. Protection from disease and infection correlates with the presence of high concentrations of EHV-1-specific IgG antibodies. Our preliminary data also shows that EHV-1-specific IgG isotypes can neutralize the virus in vitro. This suggests that IgG immediately recognizes and neutralizes infectious EHV-1 at the mucosal surface of the upper respiratory tract, thereby preventing all downstream events, such as clinical disease, nasal replication and shedding of the virus, and viremia. The overall objectives of this work are to provide mechanistic information on EHV-1 neutralization in immune horses and a better risk assessment on the potential of transmitting EHV-1 based on the immune status of a horse. Our hypothesis is that EHV-1 immune horses do not shed any infectious virus after EHV-1 infection because preexisting intranasal IgG antibodies immediately recognize the virus in the upper respiratory tract, interfere with binding to and/or block entry into nasal epithelial cells, and thereby prevent viral replication, virus shedding, and the potential to infect other horses. The hypothesis will be tested in two specific aims. Aim 1 – is to find out if immune horses that are exposed to EHV-1 can infect other EHV-1 susceptible horses. For this aim, we will experimentally infect immune horses with EHV-1 and expose them to EHV-1 susceptible horses. We will take blood and nasal secretion samples from all horses to analyze their immune response to EHV-1, and evaluate clinical signs, nasal virus shedding and cell-associated viremia to identify if infectious virus can be transmitted or not by an immune horse. Aim 2 – is to analyze the mechanistic roles of IgG antibodies on EHV-1 binding to an entry into epithelial cells. We will use cultured respiratory epithelial cells and infect them with EHV-1 in the presence or absence of different EHV-1-specific IgG isotypes to identify the neutralizing mechanism(s) by which certain IgG isotypes prevent infection. The goal of this work is to directly impact EHV-1 quarantine management by providing data for informed decision making on releasing EHV-1 immune horses earlier from quarantine.