Ross River Virus Infection: A Cross-Disciplinary Review with a Veterinary Perspective

Abstract

Ross River virus (RRV) has recently been suggested to be a potential emerging infectious disease worldwide. RRV infection remains the most common human arboviral disease in Australia, with a yearly estimated economic cost of $4.3 billion. Infection in humans and horses can cause chronic, long-term debilitating arthritogenic illnesses. However, current knowledge of immunopathogenesis remains to be elucidated and is mainly inferred from a murine model that only partially resembles clinical signs and pathology in human and horses. The epidemiology of RRV transmission is complex and multifactorial and is further complicated by climate change, making predictive models difficult to design. Establishing an equine model for RRV may allow better characterization of RRV disease pathogenesis and immunology in humans and horses, and could potentially be used for other infectious diseases. While there are no approved therapeutics or registered vaccines to treat or prevent RRV infection, clinical trials of various potential drugs and vaccines are currently underway. In the future, the RRV disease dynamic is likely to shift into temperate areas of Australia with longer active months of infection. Here, we (1) review the current knowledge of RRV infection, epidemiology, diagnostics, and therapeutics in both humans and horses; (2) identify and discuss major research gaps that warrant further research.

Exposure dynamics of Ross River virus in horses – Horses as potential sentinels (a One Health approach)

“…Results from the present study confirmed that transmission of RRV in horses in SE QLD follows a seasonal pattern with seroconversion events only being detected between December and March consistently throughout a 3.5-year period and being associated with air temperature without time-lag. In contrast, epidemiological modelling using human notification data in QLD showed that human infection peaked between March and May with rainfall, relative humidity, and air temperature identified as risk factors with 0-3 months' time-lags [5,[17][18][19][20][21][22][23][24]. Year-round irrigation usage and filled water troughs on farms and in paddocks in this subtropical study area would provide ideal breeding grounds for mosquitoes.…”

“…Various types of predictive models have been developed to identify environmental risk factors associated with increased RRV transmission. It appears that rainfall, with a lag period of 0 to 3 months, is the most frequently identified meteorological risk factor for RRV outbreaks in humans across Australia [5,[17][18][19][20][21][22][23][24]. Temperatures (both minimum and maximum) and relative humidity, with 1-2 months lags, were also frequently identified as environmental drivers for increased RRV notification in humans [18][19][20][21]23].…”

“…Ross River virus is an alphavirus, belonging to the family Togaviridae , causing most arboviral infections in Australia, with an average of around 5,000 case notifications annually [ 5 ]. RRV transmission is maintained between the reservoir host, such as marsupials (e.g., brushtail possums and wallabies), and mosquitoes [ 5 ]. Impressively, more than 40 species of mosquitoes have been identified to be capable of transmitting RRV [ 6 , 7 ].…”

Identification of 2,4-Diaminoquinazoline Derivative as a Potential Small-Molecule Inhibitor against Chikungunya and Ross River Viruses

“…RRV has recently been suggested to be a potential emerging infectious disease worldwide. RRV infection remains the most common human arboviral disease in Australia, with a yearly estimated economic cost of USD 4.3 billion [32]. The primary goal of this study was to identify small-molecule inhibitors against CHIKV, which may later be extended to identify broad-spectrum antivirals.…”

Inhibition of potassium ion channels reduces Semliki Forest virus genome replication

“…Ross River virus is also transmitted by mosquito bites and presents in a similar way to CHIKV with fever, polyarthralgia, myalgia and a rash being typical. The equine encephalitis viruses, in contrast, are associated with neurological signs as the virus predominantly targets the brain [6][7][8]. In the USA between 2012 and 2021 there were 111 confirmed cases of Eastern equine encephalitis virus infection in humans causing 46 deaths while hundreds of horses were also infected [9].…”