Kyasanur forest disease virus: viremia and challenge studies in monkeys with evidence of cross-protection by Langat virus infection

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.

Study of Kyasanur forest disease viremia, antibody kinetics, and virus infection in target organs of Macaca radiata

“…In agreement with these findings, an experimental infection studies conducted at Virus Research Centre, Pune between 1958 and 1970 found langurs to be highly susceptible to KFDV with per acute course of the disease compared to bonnet macaques. In bonnet macaques disease course was comparatively prolonged with few deaths during viremic phase and few during third week, with virus recovery from the brain similar to human biphasic disease wherein fever and signs of neurological manifestations are reported in third week 12 . Another study in bonnet macaques demonstrated, virus-specific gastrointestinal and lymphoid lesions and viral antigens in these same organs by immunohistochemistry in experimentally infected animals 11 .…”

Evaluation of Macaca radiata as a non-human primate model of Dengue virus infection

“…Bonnet monkeys ( M. radiata ) are indigenous to Southern India, where DENV circulates widely. In previous studies, Kyasanur forest disease virus (KFDV), tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and West Nile virus (WNV) have been inoculated into bonnet monkeys, resulting in high viraemia 23 – 25 . Furthermore, neutralisation antibodies have been detected after natural infection in bonnet monkeys 26 .…”

Historical Expansion of Kyasanur Forest Disease in India From 1957 to 2017: A Retrospective Analysis

“…The live attenuated vaccine was also tested among langurs, and although the vaccine prevented death, it could not protect against challenge infection (Bhatt & Dandawate, ; Pattnaik, ). Additionally, an attenuated Langat virus vaccine ( Langat virus is related to KFDV as they are both part of the tick‐borne encephalitis virus complex) was also tested among langurs and was found to show protection against KFDV among monkeys (Shah et al, ; Thind, ).…”