Equine infectious anaemia

Previous author: RF COOK AND CJ ISSEL

Current authors:

C LEROUX
Research Director, Viral Infections and Comparative Pathology, UMR 754 INRAE EPHE Lyon 1 University, 50 Avenue Tony Garnier, Lyon, 69007, France

JL CADORE
Professor in internal medicine, DVM, PhD, Viral Infections and Comparative Pathology, UMR 754 INRAE EPHE Lyon 1 University, 1 Avenue Bourgelat, Marcy-L'Etoile, 69280, France

GENERAL INTRODUCTION: RETROVIRIDAE

Introduction

Equine infectious anaemia (EIA) is a disease of domestic Equidae (horses, ponies, mules, donkeys) that is caused by equine infectious anaemia virus (EIAV), a retrovirus classified in the genus Lentivirus of the family Retroviridae. Like other retroviruses, EIAV is responsible for a chronic lifelong infection; most infected equids are inapparent carriers, able to control viral replication without developing overt signs of disease. Equine infectious anaemia has an almost worldwide distribution and is a significant threat to the equine industry, evidenced by its classification as one of the eleven notifiable equine diseases listed by the OIE (the World Organisation for Animal Health).

The disease was first reported in France in 1843⁷³ and its full description, first published in 1904 included the different stages of the disease and its transmissible nature by a “filterable agent”.¹¹⁵ For over five decades, research in EIA suffered from the lack of any in vitro culture system. Fortunately, during the late 1960s, Japanese investigators developed leukocyte culture systems that were able to propagate EIAV.⁶³ The discovery of insect transmission of EIAV^{33, 39, 40, 54} and the development of the first diagnostic test^{22, 23} were key steps for the management of EIAV infection. The discovery of human immunodeficiency virus (HIV), an EIAV-related lentivirus, renewed interest in the equine virus.

Clinical signs of EIA are generally non-specific and vary considerably between individual animals and possibly even between equid species,²⁶ making the differential diagnosis often complicated. Although equids remain infected with EIAV for life, most are able to control viral replication to such an extent they are free from overt signs of disease and are therefore classified as “inapparent carriers”.^{29, 30, 45} These "clinically invisible" infected equids contribute to unintended spread of the infection and disease. Since the first vaccine trial in Canada in 1945⁵ and in Japan in the early 1970s, many vaccine strategies/approaches have been developed that all failed to efficiently protect horses against infection from heterologous strains of EIAV. In contrast, however, extensive immunization of equids in China with a live attenuated EIAV strain has had a reported beneficial effect by limiting disease progression in infected equids.¹¹⁶ In much of the world, EIA control still relies on the identification and removal or quarantine of infected animals; EIAV-infected animals are identified using serological surveillance.

Aetiology

The infectious nature of EIA has been known since 1904,¹¹⁵ which places it among the first diseases proven to be caused by a virus. After their initial report of the infectious nature of this disease present in the Meuse region of eastern France, Vallée and Carré described the culture of the virus by successive passage (unfortunately lost subsequently), the blood-borne transmission of EIAV infection, the susceptibility of donkeys to infection, the fact that anaemia was not the only expression of the disease (these investigators noted that “infectious anaemia” was not an appropriate designation for the disease as it did not convey correctly the complexity of the disease entity they observed), and the cyclic nature of the disease. They anticipated that prophylaxis would be complicated by the blood-borne nature of agent transmission, and the presence of horses infected without clinical expression of disease. With the discovery of the Rous sarcoma virus in chickens,⁹⁸ during the twentieth century.

Members of the family Retroviridae are ancient viruses that probably emerged during the early Palaeozoic era^{2, 47} more than 450 million years ago, thus they are probably as old as their jawed vertebrate hosts.² While retroviruses are present in a wide host range, from fish to humans, lentiviruses are limited to equids, cattle, small ruminants, wild and domestic Felidae, non-human primates and humans, suggesting they arose "only" one million years ago, thus relatively recently in evolutionary terms.¹²⁰

Retroviruses are enveloped RNA viruses (80–100 nm in diameter). Their genomes (~8 to 11 kb) consist of a dimer of linear, single-stranded, positive-sense RNAs. Importantly, their replication is dependent on the reverse transcriptase (RT) enzyme, which is an RNA-dependent DNA polymerase that converts positive-sense viral RNA into DNA during the early stage of infection. Equine infectious anaemia virus shares morphological, antigenic and genetic features with small ruminant lentiviruses (SRLVs)⁶⁷ (see Caprine arthritis-encephalitis and Visna-maedi) and HIV. This equine retrovirus (EIAV) has been described as the “country cousin” of HIV⁶⁵ because, like its more infamous relative, it is classified in the genus Lentivirus (subfamily Orthoretrovirinae) within the family Retroviridae. Early description of HIV reported on the antigenic similarities between the gag proteins of the human LAV/HTLV-III virus and that of EIAV...