EHV-1: A Constant Threat to the Horse Industry

Abstract

Equine herpesvirus-1 (EHV-1) is one of the most important and prevalent viral pathogens of horses and a major threat to the equine industry throughout most of the world. EHV-1 primarily causes respiratory disease but viral spread to distant organs enables the development of more severe sequelae; abortion and neurologic disease. The virus can also undergo latency during which viral genes are minimally expressed, and reactivate to produce lytic infection at any time. Recently, there has been a trend of increasing numbers of outbreaks of a devastating form of EHV-1, equine herpesviral myeloencephalopathy. This review presents detailed information on EHV-1, from the discovery of the virus to latest developments on treatment and control of the diseases it causes. We also provide updates on recent EHV-1 research with particular emphasis on viral biology which enables pathogenesis in the natural host. The information presented herein will be useful in understanding EHV-1 and formulating policies that would help limit the spread of EHV-1 within horse populations.

Keywords: EHV-1; abortion; horse; latency; myeloencephalopathy.

FIGURE 1

Schematic illustration of EHV-1 structure. The basic architecture of EHV-1 consists of an envelope, a tightly woven dsDNA genome enclosed within the capsid, and a tegument layer. Several glycoproteins are present on the surface of the envelope.

FIGURE 2

Lytic life cycle of EHV-1. The virus enters susceptible cells either by fusion at the cell membrane or by the non-classical endocytosis pathway. This is followed by the release of nucleocapsid into the cytoplasm of an infected cell. The nucleocapsid, which is transported to the nucleus via dynein, docks at the NPC and extrudes the viral DNA directly into the nucleus. This initiates viral gene expression beginning with the transcription of IE (α) gene. Immediate early proteins are then synthesized in the cytoplasm and migrate to the nucleus where they direct the transcription of E (β) genes. Early proteins, synthesized in the cytoplasm, translocate to the nucleus to initiate virus DNA replication and virus L (γ) gene expression. Next, some of the L proteins synthesized in the cytoplasm, migrate to the nucleus to form the capsid before encapsidation of the new virus DNA. The newly assembled virion then migrates through the nucleus and the cytoplasmic membranes before it is eventually released outside of the cell.

FIGURE 3

Herpesvirus capsid formation. The basic assembly of a matured capsid consists of complex formation between major capsid protein and scaffold protein with the incorporation of a portal protein. An early step in the formation of a spherical procapsid (partial procapsids) involves complex interactions between the major capsid protein and the scaffold protein to produce what, first, looks like an angular segment. A complex of portal and scaffold protein is incorporated with the progressive enlargement of the partial procapsid. Once the procapsid is formed, virus DNA is packaged marking the exit of the scaffolding proteins creating a polyhedral shape.

FIGURE 4

Herpesvirus egress pathway. Following intranuclear encapsidation of the virus genome, the herpesviral nucleocapsid will bud through the inner nuclear membrane resulting in perinuclear localization of an enveloped primary virion. This primary envelope becomes lost (de-envelopment) as the virus translocates into the cytosol where the nucleocapsid acquires tegument proteins. Final (secondary) envelopment then occurs in the cytoplasm derived from the trans-Golgi network and the enveloped virion is transported in a vesicle to the plasma membrane for release.

FIGURE 5

Schematic illustration of EHV-1 pathogenesis. EHV-1 primarily infects the respiratory epithelial cells. The virus can cross the basement membrane and invade the lamina propria where it infects circulating leucocytes. The virus then travels through the lymphatic system to regional lymph nodes where it undergoes amplification and infects peripheral blood mononuclear cells leading to a state of cell-associated viremia. The cell-associated viremia ensures that EHV-1 is disseminated to distant sites such as the endometrium of the pregnant uterus and the CNS causing inflammatory responses that culminate in the development of pathologies; abortion and EHM.