Open Access Research

Susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, Aotus nancymaae

Erik J Reaves1, Gabriela Salmón-Mulanovich1, Carolina Guevara1, Tadeusz J Kochel1, Thomas J Steinbach2, David E Bentzel1 and Joel M Montgomery1*

Author Affiliations

1 Naval Medical Research Unit No. 6, Av. Venezuela cdra. 36 s/n, Callao 2, Peru

2 Walter Reed Army Institute of Research, 503 Robert Grant Av, Silver Spring, MD, 20910-7500, USA

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Virology Journal 2012, 9:95  doi:10.1186/1743-422X-9-95

Published: 21 May 2012

Abstract

Background

Rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus Lyssavirus. Little is known about rabies virus infection in species of New World non-human Primates (NHP). To investigate the suitability of the owl monkey Aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isolation, and PCR to evaluate the incubation period, immunity, and pathogenesis of infected animals. We tested the hypothesis that no viremic state exists for rabies virus.

Methods

Eight monkeys divided into two equal groups were inoculated intramuscularly either in the neck or footpad with 105 pfu of rabies virus (Pasteur/V-13R) and observed for >130 days. Oral and blood samples were collected and analyzed.

Results

Two monkeys inoculated in the neck displayed classic paralytic rabies. The mean incubation period was 11.5 days. The average maximum IgG response (antibody titer >0.200 O.D.) was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical rabies cases, respectively (p = 0.0429). No difference in IgM or IgG time to seroconversion or average maximum IgM level was observed between neck versus footpad inoculation groups. No viremia or viral shedding was detected by PCR or viral isolation during the observation period, including within the two symptomatic animals three days after disease onset. Tissue sections examined were unremarkable for inflammation or other histologic signs of rabies within the asymptomatic animal. Similarly none of the brain sections exhibited immunoreactivity for rabies virus antibody.

Discussion

This study demonstrates there is no difference in time to immune response between inoculation sites and distance to the brain; however, immune response tends to be more rapid in cases of clinically apparent disease and prolonged in cases infected at sites further from the brain.

Conclusions

Our findings support the hypothesis that a viremic state for rabies does not exist in the New World Monkey, Aotus nancymaae, and it appears that this species may be refractory to infection. The species does provide a suitable model to assess post infection immune responses. Additional studies that address the limitations of sample size, length of observation, and lack of measurable infection should be conducted.

Keywords:
Rabies; Rhabdovirus; Lyssavirus; Incubation period; Viremia; Monkey; Aotus nancymaae; Non-human Primate; Ante mortem; Vaccine