Abstract
Kyasanur Forest Disease Virus (KFDV), discovered in 1957, is a member of the tick-borne encephalitis virus (TBEV) complex. Diseases caused by members of the TBEV complex occur in many parts of the world. KFDV produces a hemorrhagic fever in humans in South India and fatal illnesses in both species of monkeys in the area, the black faced langur (Presbytis entellus) and the bonnet macaque (Macaca radiata). Experimental infection of the langur and the bonnet macaque with early mouse passage KFDV strain P9605 resulted in a viremia of up to 11 days duration, peak viremia titers as high as 10 9, and death in 82 = 100% of the animals. Prolonged passage of the KFDV strain P9605 in monkey kidney tissue culture resulted in a markedly reduced virulence of the virus for both species; peak viremia titers in monkeys decreased by 2.5 to 4.0 log LD 50 (p= 0.001), and the mortality decreased to 10% (p= 0.001). In challenge experiments, monkeys previously infected with tissue-culture-adapted KFDV, or with the related Langat virus from Malaysia, were fully protected against virulent KFDV. These studies in non-human primates lend support to the idea that a live virus vaccine from a member of the TBEV complex may be broadly protective against infections by other members of the TBEV complex.
Highlights
Flaviviruses of the tick-borne encephalitis virus (TBEV) complex are widely and focally distributed in nature
We show here that 1) Kyasanur Forest Disease Virus (KFDV) produces a high-titered viremia and death in both species of monkeys that inhabit the endemic area, 2) a TC-adapted KFDV has markedly reduced virulence for both monkey species, and 3) monkeys previously infected with TC-adapted KFDV or with heterologous Langat virus (LGTV) completely resist challenge with virulent KFDV
Animal model for KFDV pathogenesis Both the black-faced langur and the red-faced bonnet appear to be good models to study KFDV infection. Both species are naturally infected by KFDV in the endemic forested area in south India and many succumb to the disease[16,17]
Summary
Flaviviruses of the tick-borne encephalitis virus (TBEV) complex are widely and focally distributed in nature. New viruses of the complex and illnesses associated with them are frequently being described from different parts of the world. Human illnesses associated with infections with these viruses include mild or severe encephalitis and hemorrhagic fevers[1]. Omsk Hemorrhagic Fever Virus (OHFV), which is endemic in western Siberia, Russia, and recognized as a tick-borne flavivirus in 1947, is distantly related to KFDV1. In addition to the hemorrhagic fevers noted above, viruses of the TBEV complex are responsible for over 10,000 cases of encephalitis, annually, in Europe and Asia, and for localized illnesses in different parts of the world[1]
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