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

Dilip R Patil,Rima R Sahay,Himanshu Kaushal,Rajlaxmi Jain,Siddharam Fulari,Triparna Majumdar,Sandeep Kumar,Manoj Kadam,Annasaheb Suryawanshi,Sreelekshmy Mohandas,Pravin Kore,Pragya D Yadav ,Anita M Shete ,Gouri Chaubal,Prasad Sarkale,Savita Patil,Prachi Pardeshi ,Chandrashekhar Mote,Rajen Lakra,Devendra T Mourya

doi:10.1038/s41598-020-67599-x

Abstract

The present manuscript deals with experimental infections of bonnet macaques (Macaca radiata) to study disease progression for better insights into the Kyasanur Forest Disease (KFD) pathogenesis and transmission. Experimentally, 10 monkeys were inoculated with KFD virus (KFDV) (high or low dose) and were regularly monitored and sampled for various body fluids and tissues at preset time points. We found that only 2 out of the 10 animals showed marked clinical signs becoming moribund, both in the low dose group, even though viremia, virus shedding in the secretions and excretions were evident in all inoculated monkeys. Anti-KFDV immunoglobulin (Ig)M antibody response was observed around a week after inoculation and anti-KFDV IgG antibody response after two weeks. Anaemia, leucopenia, thrombocytopenia, monocytosis, increase in average clotting time, and reduction in the serum protein levels were evident. The virus could be re-isolated from the skin during the viremic period. The persistence of viral RNA in the gastrointestinal tract and lymph nodes was seen up to 53 and 81 days respectively. Neuro-invasion was observed only in moribund macaques. Re-challenge with the virus after 21 days of initial inoculation in a monkey did not result in virus shedding or immune response boosting.

Highlights

The present manuscript deals with experimental infections of bonnet macaques (Macaca radiata) to study disease progression for better insights into the Kyasanur Forest Disease (KFD) pathogenesis and transmission
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 KFD virus (KFDV) with per acute course of the disease compared to bonnet macaques
The high dose group was inoculated with 1 05.57 tissue culture infective dose 50 (TCID50) of KFDV, low dose group with 1 03.57 TCID50 and control with uninfected Baby hamster kidney (BHK)-21 cell supernatant of the same passage by subcutaneous (s/c) route (1 ml) below the nape of the neck under sedation

Summary

Introduction

The present manuscript deals with experimental infections of bonnet macaques (Macaca radiata) to study disease progression for better insights into the Kyasanur Forest Disease (KFD) pathogenesis and transmission. Presbytus entellus (Black faced langur) and Macaca radiata (Bonnet macaque), which are abundant in the Western Ghats region of India, are the most affected species of animals; acting as sentinels for the virus spread in an area[10,11] The susceptibility of both the species has been proven experimentally too[11,12,13]. A decade long study conducted on monkey mortality in KFD endemic area revealed that, out of 1,046 deaths, 860 were P. entellus and only 186 were M. radiata with virus isolation percentage of 50% and 18.05% in necropsied animals respectively[17] 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. The above studies confirmed the suitability of bonnet macaque as a model to study viscerotropic KFD seen in humans

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