Each year, RRV and BFV are together responsible for thousands of human infections in Australia.Viruses from the SINV group use birds as their main amplifying hosts and in Scandinavia hundreds of human cases are reported annually (Figure 1) .The Old World alphaviruses include the Sindbis virus (SINV) group, Barmah Forest virus (BFV), O’nyong’nyong virus (ONNV), Ross River virus (RRV), Semliki Forest virus (SFV), and chikungunya virus (CHIKV) and can cause symptoms of high fever, rash, incapacitating arthralgia, and chronic arthritis [5,6].Alphaviruses can have a very diverse vertebrate and invertebrate host range .Alphavirus replication is relatively fast, resulting in acute disease in vertebrate hosts and strong cytopathic effects in vertebrate cell culture.In contrast, infection of mosquito cells results in persistent infection and shows little to no sign of fitness loss in infected mosquitoes.
Briefly, ns P1 is the membrane anchor of the replication complex (RC) and possesses guanine-7-methyltransferase (MTAse) and guanylyl transferase activities necessary for capping of the viral RNA [20,21].
The mosquito-borne alphaviruses are generally subdivided based on their geographic origin.
The New World alphaviruses include Venezuelan, Western, and Eastern equine encephalitis viruses (V/W/E-EEV) and are mostly associated with encephalitic disease in horses and humans.
Ns P4 is the RNA-dependent RNA polymerase [24,25], which is the first ns P to be proteolytically cleaved from the polyprotein.
Together with the remaining ns P123 peptide, ns P4 forms a short-lived RC that produces the complementary negative-sense ((−)RNA).