, 2011). It has been hypothesized that OROV persists in sylvatic endemic cycles of transmission, although these remain poorly characterized and may involve multiple vectors and reservoir hosts (Pinheiro et al., 1981a). Investigation of candidate vector(s) has centered upon mosquitoes, but although isolations of OROV have been made from Aedes serratus and Coquillettidia venezuelensis ( Anderson et Duvelisib al., 1961 and Pinheiro et al., 1981a), the number of successful recoveries of the virus has been

extremely low. The challenge of making positive isolations of OROV from adult vectors under endemic scenarios is illustrated by the isolation of only a single strain of the virus from processing over 1 million mosquitoes, phlebotomine sandflies, ticks and other ectoparasites in the Amazon region during inter-epidemic periods ( Pinheiro et al., 1981a). Screening of potential reservoir hosts for OROV has also been undertaken but remains inconclusive, with antibodies to infection detected in a wide range of domestic and wild avian species, primates, wild carnivores and rodents ( Batista et al., 2012 and Pinheiro et al., 1981a). Isolations of OROV, that may be indicative of a transmissible find protocol viraemia, have also been made from a sloth Bradypus tridactylus ( Pinheiro et al., 1962) and a sylvatic monkey Callithrix sp. ( Nunes et al., 2005). Replication and concurrent clinical signs also occur in the golden hamster (Mesocricetus auratus),

which is currently used as an experimental model ( Pinheiro et al., 1982 and Rodrigues et al., 2011). Interestingly, the ability of OROV to replicate in livestock appears not to have been addressed in studies to date, as major outbreak areas of disease have not coincided

with centers of ruminant production. In contrast to the theoretical sylvatic cycle, epidemic transmission of OROV between humans as an anthroponosis are well characterized, being driven almost exclusively by C. paraensis. The role of this species as a vector of OROV has been investigated in both the field ( Roberts et al., 1981) and in the laboratory ( Pinheiro et al., 1982 and Pinheiro et al., 1981b). The latter studies are notable for convincingly demonstrating biological transmission of OROV between hosts by Culicoides and are among the most complete vector competence trials of the genus. Larvae of C. paraensis develop in microhabitats of decomposing banana and plantain stalks and stumps and cacao Histone demethylase hulls ( Hoch et al., 1986) ( Fig. 1F), having originally exploited rotting organic material in dry tree-holes, leaf debris and damp soil for this purpose ( Mercer et al., 2003, Pappas et al., 1991 and Wirth and Felippe-Bauer, 1989). Following fruit harvesting, these waste products accumulate in close proximity to high-density human housing, resulting in biting attacks ofC. paraensis adult females on inhabitants. Unlike the majority of other Culicoides species that have a primarily crepuscular (dusk and dawn) periodicity ( Kettle, 1977 and Mellor et al.