Old World alphavirus infections in animals

Introduction

Alphaviruses in the family Togaviridae are important emerging and re-emerging pathogens of humans and animals. These viruses can be divided into the New World alphaviruses (see Equine encephalitides caused by alphaviruses in the Western Hemisphere) that are associated with encephalitis in horses, humans and certain other animals in the Americas, and the Old World alphaviruses, which are mostly believed to be associated with arthralgia in humans, with less data available as to their importance in animals. Recent reports of infections in horses with Old World alphaviruses such as Middelburg virus (MIDV) and Sindbis virus (SINV) in South Africa and Ross River virus (RRV) in Australia have renewed interest in the potential of these viruses as animal pathogens. This chapter focuses on the lesser known alphaviruses, in particular the Old World alphaviruses and their role in animal diseases.

Aetiology and epidemiology

The group of alphaviruses includes 31 recognized species grouped into 8 antigenic complexes (Figure 1) based on their serological cross-reactions: Barmah Forest, Eastern equine encephalitis, Middelburg, Ndumu, Semliki Forest, Trocara, Venezuelan equine encephalitis and Western equine encephalitis complexes. These viruses have a very wide geographic distribution.^{21, 75} (see Table 1 Equine encephalitides caused by alphaviruses in the Western Hemisphere). Following the full genome sequencing of all members of the alphaviruses, it has been suggested that the alphaviruses emerged in the southern oceans from marine animals, with subsequent spread to terrestrial vertebrate hosts and mosquito vectors. This enabled them to expand their range throughout the Old and New World, where reintroductions between continents have also occurred.¹⁸ The molecular biology of the genus is described in detail elsewhere (see Equine encephalitides caused by alphaviruses in the Western Hemisphere). Although much less is known about the pathogenic potential of the Old World viruses for animals, reports on human and animal disease, reservoir hosts, vectors, and laboratory investigations are summarized in this chapter.

Figure 1 Phylogenetic tree of representative isolates of all alphavirus species in the genus a Alphavirus, family Togaviridae as reproduces from the ICTV website (https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/togaviridae). The tree was generated from a conserved region of envelope protein gene nucleotide sequences (2184 nt) using the GTR+I+Γ substitution model and Maximum likelihood method and mid-point rooted. Bootstrap values above 70 generated by 1000 replicates of neighbour-joining tree are indicated next to the main branches.¹⁰

Except for the salmon pancreatic disease virus (SPDV), sleeping disease virus (SDV) and the Southern elephant seal virus (SESV), members of the Alphavirus genus are mainly transmitted by haematophagous arthropods, especially mosquitoes, The salmon pancreatic disease virus has been detected in sea lice (Lepeophtheirus salmonis and Lepeophtheirus macrorhini). The vectors for SESV have not been confirmed as yet.^{18, 37, 76} Studies on the complete genome sequences of all known members of the genus suggest that SPDV and SESV form a separate group to the latter and may be the common ancestor of alphaviruses. The mosquito-transmitted viruses are classified into two well-defined monophyletic groups: New World/encephalitic viruses and the Old World/arthralgia viruses.

The New World viruses consist of the Western equine encephalitis virus (WEEV), SINV, Eastern equine encephalitis virus (EEV) and Venezuelan equine encephalitis virus (VEEV) complexes. Apart from SINV, which occurs worldwide and mostly cause mild disease, the rest of the New World viruses occur in North and South America and are associated with encephalitis in horses and humans (see Equine encephalitides caused by alphaviruses in the Western Hemisphere). Recombination events between EEV and SINV are thought to have given rise to the WEE complex and more pathogenic viruses.⁷

The Old World viruses are grouped into three complexes, namely MIDV, Ndumu (NDUV), Barmah Forest virus (BFV) and Semliki Forest virus (SFV). These viruses are mainly associated with epidemics of polyarthritis in Asia, Australia, Europe, and Africa.¹⁸  Middelburg virus has recently been associated with neurological signs and possibly signs of arthralgia in horses in South Africa.⁷²

Table 1 lists alphaviruses that cluster within the Old World monophyletic groups as well as Sindbis in the WEE group with potential clinical significance in humans and animals.

Table 1: Old World alphaviruses and others outside of the Americas