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

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.

Absence of accessory genes in a divergent simian T-lymphotropic virus type 1 isolated from a bonnet macaque (Macaca radiata).

BACKGROUND: Primate T-lymphotropic viruses type 1 (PTLV-1) are complex retroviruses infecting both human (HTLV-1) and simian (STLV-1) hosts. They share common epidemiological, clinical and molecular features. In addition to the canonical gag, pol, env retroviral genes, PTLV-1 purportedly encodes regulatory (i.e. Tax, Rex, and HBZ) and accessory proteins (i.e. P12/8, P13, P30). The latter have been found essential for viral persistence in vivo. METHODOLOGY/PRINCIPAL FINDINGS: We have isolated a STLV-1 virus from a bonnet macaque (Macaca radiata-Mra18C9), a monkey from India. The complete sequence was obtained and phylogenetic analyses were performed. The Mra18C9 strain is highly divergent from the known PTLV-1 strains. Intriguingly, the Mra18C9 lacks the 3 accessory open reading frames. In order to determine if the absence of accessory proteins is specific to this particular strain, a comprehensive analysis of the complete PTLV-1 genomes available in Genbank was performed and found that the lack of one or many accessory ORF is common among PTLV-1. CONCLUSION: This study raises many questions regarding the actual nature, role and importance of accessory proteins in the PTLV-1 biology.

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

Dengue virus (DENV) causes a wide range of illnesses in humans, including dengue fever and dengue haemorrhagic fever. Current animal models of DENV infection are limited for understanding infectious diseases in humans. Bonnet monkeys (Macaca radiata), a type of Old World monkey, have been used to study experimental and natural infections by flaviviruses, but Old World monkeys have not yet been used as DENV infection models. In this study, the replication levels of several DENV strains were evaluated using peripheral blood mononuclear cells. Our findings indicated that DENV-4 09-48 strain, isolated from a traveller returning from India in 2009, was a highly replicative virus. Three bonnet monkeys were infected with 09-48 strain and antibody responses were assessed. DENV nonstructural protein 1 antigen was detected and high viraemia was observed. These results indicated that bonnet monkeys and 09-48 strain could be used as a reliable primate model for the study of DENV.

Cercopithecine herpesvirus 1 risk in a child bitten by a Bonnet Macaque monkey.

BACKGROUND: Exotic animal importation and trade has the potential to expose the public to a variety of injuries and diseases not endemic to the United States. Bonnet Macaque monkeys are a fairly common primate illegally held in captivity. These monkeys become aggressive as they age past 2 years and are known to carry asymptomatic Cercopithecine herpesvirus 1 infection. OBJECTIVE: This case is presented to illustrate the point that simple wound management alone may not only be insufficient but could be fatal in certain exotic animal bites and that the emergency physician should consult with authorities familiar with exotic animals when treating a patient with an exotic animal bite. CASE REPORT: We present the case of a 2-year-old child that was bitten by his neighbor's pet Bonnet Macaque monkey. This species of Old World monkey carries the Cercopithecine herpesvirus 1 (simian B virus) 73-100% of the time. This infection in humans can lead to an encephalitis that has a 70% mortality rate. Consultation with animal authorities led to the proper treatment, which included routine wound care, rabies prophylaxis, irrigation with sodium hypochlorite solution, and treatment with antiviral medication. CONCLUSION: Simple wound management alone may not be enough in patients bitten by exotic animals. Consultation with local zoo officials, veterinary medical schools, or the Centers for Disease Control and Prevention is recommended in these cases.

Sabin attenuated LSc/2ab strain of poliovirus spreads to the spinal cord from a peripheral nerve in bonnet monkeys (Macaca radiata).

Vaccine-associated paralytic poliomyelitis is a serious concern while using the live attenuated oral polio vaccine for the eradication of poliomyelitis. The bonnet monkey model of poliovirus central nervous system (CNS) infection following experimental inoculation into the ulnar nerve allows the comparative study of wild-type and attenuated poliovirus invasiveness. Dosages >/=10(4) TCID(50) of Mahoney strain of poliovirus type 1 [PV1(M)] result in paralysis. In contrast, even with 10(7) TCID(50) of Sabin attenuated strain of poliovirus type 1 (LSc/2ab), no paralysis occurs, but virus spreads into the CNS where viral RNA is found in spinal cord neurons. While wild-type PV1(M) viral RNA replicates in neurons (and possibly in glial cells) and in cells around vessel walls, which may be mononuclear or endothelial cells, attenuated viral RNA is detected only in neurons. Systemic viraemia and gastrointestinal virus shedding occurs only in PV1(M)-infected animals. While a systemic serologic response is detected in both groups of animals, cerebrospinal fluid antibodies are detected only in animals infected with PV1(M). Both the PV1(M) and LSc/2ab strains spread to the cervical spinal cord and then to the lumbar spinal cord following ulnar nerve inoculation. Neuronophagia and neuronal loss are only seen in PV1(M)-infected monkeys in whom clinical paralysis is observed. Infection with LSc/2ab does not result in neuronophagia, neuronal loss or clinical paralysis. Spread of attenuated poliovirus in spinal cord neurons without causing paralysis following inoculation into the ulnar nerve is an important finding.

Respiratory syncytial virus infects the Bonnet monkey, Macaca radiata.

The Bonnet monkey model of respiratory syncytial virus (RSV) infection may be a useful nonhuman primate model for studying RSV disease in humans because Bonnet monkeys can predictably be infected to obtain an orderly sequence of morphologic, cytologic, virologic, serologic, and inflammatory changes related to time of infection. Young feral Bonnet monkeys, Macaca radiata, were infected endotracheally with 10(6) plaque-forming units (pfu) of the Long strain of RSV. RSV was recovered from the animals' lungs at necropsy on days 3, 5, and 7 with the highest viral titer obtained on day 3 (1.1 and 5.2 x 10(3) pfu/g of tissue in the upper and lower lobes, respectively). RSV antigen and F protein mRNA were detected 3-5 days after infection in alveolar macrophages and in the epithelium of bronchi, terminal bronchioles, and alveoli. Histologic analysis of RSV-infected lungs at necropsy revealed progressive bronchiolar mucosal and submucosal inflammation, periarterial mononuclear interstitial inflammation, and focal alveolitis, with a maximal response at 7 days after infection. Cell counts in bronchoalveolar lavage (BAL) increased with time with neutrophils and macrophages predominating on day 3 (6.47 and 5.85 x 10(5)/mm3, respectively) and lymphocytes predominating on day 9 (4.18 x 10(5)/mm3). Serum-neutralizing antibody appeared on day 5 and IgG antibody to RSV was detected on day 9. This sequence of morphologic, cytologic, virologic, serologic, and inflammatory change following RSV infection creates a useful model in the study of experimentally induced RSV disease with a potential for testing future vaccine-induced alterations in RSV disease response.