GENETIC-CONTROL OF HOST-RESISTANCE TO FLAVIVIRUS INFECTION IN ANIMALS

Flaviviruses are small, enveloped RNA viruses which are generally tran smitted by arthropods to animals and man. Although flaviviruses cause important diseases in domestic animals and man, flaviviral infection o f animals which constitute the normal vertebrate reservoir may be mild or sub-clinical, which suggests that some adaptation between virus an d host may have occurred. While this possibility is difficult to study in wild animals, extensive studies using laboratory mice have demonst rated the existence of innate, flavivirus-specific resistance. Resista nce is heritable and is attributable to the gene my: which is located on chromosome 5 in this species. The mechanism of resistance is at pre sent unknown, but acts early and limits the replication of flaviviruse s in cells. While some evidence supports a role for Flv(r) in enhancin g the production of defective interfering virus, thereby restricting t he production of infectious virus, other reports suggest that Flv(r) i nterferes with either virus RNA replication or RNA packaging. Recent r esearch suggests that cytoplasmic proteins bind to the viral replicati on complex and that allelic forms of these proteins in resistant mice may restrict the production of infectious progeny. Apparent resistance to flaviviruses has been described in other vertebrates, although it remains to be seen if this is attributable to a homologue of Flv(r). N onetheless, knowledge gained of the characteristics and function of Fl v(r) in mice should be applicable to other host species, and improveme nt of resistance to flaviviral infection in domestic animals by select ive breeding or gene technology may ultimately be possible.