Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul 28;10(1):12561.
doi: 10.1038/s41598-020-67599-x.

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

Dilip R Patil  1 , Pragya D Yadav  1 , Anita Shete  1 , Gouri Chaubal  1 , Sreelekshmy Mohandas  1 , Rima R Sahay  1 , Rajlaxmi Jain  1 , Chandrashekhar Mote  2 , Sandeep Kumar  1 , Himanshu Kaushal  1 , Pravin Kore  1 , Savita Patil  1 , Triparna Majumdar  1 , Siddharam Fulari  1 , Annasaheb Suryawanshi  1 , Manoj Kadam  1 , Prachi G Pardeshi  1 , Rajen Lakra  1 , Prasad Sarkale  1 , Devendra T Mourya  3
Affiliations

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

Dilip R Patil et al. Sci Rep. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Bonnet macaque sacrifice time points. Each bar (yellow: low dose, blue: high dose) represents the days on which monkeys were sacrificed post KFDV inoculation. Monkeys which became moribund are highlighted with an asterisk. All the monkeys were inoculated with KFDV on day 0 and BM-6 was re-inoculated on day 21.
Figure 2
Figure 2
Clotting time. Comparison of average clotting time values at different days post KFDV inoculation. The group sizes at day 0, 3, 6, 10, 14, 20 days post inoculation were 10, 9, 9, 6, 5 and 4 respectively and thereafter 1 animal each.
Figure 3
Figure 3
Graphs represent the copy number of KFDV RNA in serum (red line), stool (violet bar) and urine (green bar) (primary y axis) and P/N values of anti-KFDV IgM (orange line) and IgG (blue line) ELISA (secondary y axis) in each macaque at days post KFDV inoculation.
Figure 4
Figure 4
Histopathological observations. (a) Mucosal ulceration and focal mononuclear infiltration in small intestine, H&E, × 100, (b) mononuclear cell infiltration in the small intestine, H&E × 200, (c) sub-mucosal congestion in the large intestine, H&E × 100, (d) submucosal congestion in the large intestine, H&E, × 200.
Figure 5
Figure 5
Immunohistochemistry. (a) Stomach: cytoplasmic immunostaining of glandular cells, DAB × 200, (b) Small intestine: immunostaining of intestinal mucosa, DAB × 200. (c) Large intestine: immunostaining of epithelium, DAB × 200, (d) Spleen: immunostaining of splenic white pulp, DAB × 200, (e) Skin: immunostaining of epidermis layer, DAB × 200.
Figure 6
Figure 6
Cytokine analysis. Profile of IL-6 secretion of KFDV stimulated splenocytes in different macaques at sacrifice.
See this image and copyright information in PMC

References

    1. Work TH, Trapido H. Kyasanur forest disease a new virus disease in India: Summary of the preliminary report of investigations of the Virus Research Centre on an epidemic disease affecting forest villagers and wild monkeys of Shimoga district, Mysore. Indian J Med Sci. 1957;11:1–2. - PubMed
    1. Mourya DT, Yadav PD. The recent scenario of the emergence of Kyasanur forest disease in India and public health importance. Curr. Trop. Med. Rep. 2016;3:7–13.
    1. Work TH, Roderiguez FM, Bhatt PN. Virological epidemiology of the 1958 epidemic of Kyasanur Forest disease. Am. J. Public Health Nations Health. 1959;49:869–874. - PMC - PubMed
    1. Jorge Boshell, M., Rajagopalan, P.K., Goverdhan, M.K. & Pavri, K.M. The isolation of Kyasanur forest disease virus from small mammals of the SagaSorab forests, Mysore state, India. Indian J. Med. Res.56(4), 569–72 (1968). - PubMed
    1. Rajagopalan PK, Paul SD, Sreenivasan MA. Involvement of Rattus blanfordi (rodentia: muridae) in the natural cycle of Kyasanur forest disease virus. Indian J Med. Res. 1969;57(6):999–1002. - PubMed

MeSH terms

LinkOut - more resources