Bacterial Infections in Pigs Experimentally Infected with Nipah Virus

Abstract

Nipah virus (NiV; Paramyxoviridae) caused fatal encephalitis in humans during an outbreak in Malaysia in 1998/1999 after transmission from infected pigs. Our previous study demonstrated that the respiratory, lymphatic and central nervous systems are targets for virus replication in experimentally infected pigs. To continue the studies on pathogenesis of NiV in swine, six piglets were inoculated oronasally with 2.5 x 10(5) PFU per animal. Four pigs developed mild clinical signs, one exudative epidermitis, and one neurologic signs due to suppurative meningoencephalitis, and was euthanized at 11 days post-inoculation (dpi). Neutralizing antibodies reached in surviving animals titers around 1280 at 16 dpi. Nasal and oro-pharyngeal shedding of the NiV was detected between 2 and 17 dpi. Virus appeared to be cleared from the tissues of the infected animals by 23 dpi, with low amount of RNA detected in submandibular and bronchial lymph nodes of three pigs, and olfactory bulb of one animal. Despite the presence of neutralizing antibodies, virus was isolated from serum at 24 dpi, and the viral RNA was still detected in serum at 29 dpi. Our results indicate slower clearance of NiV from some of the infected pigs. Bacteria were detected in the cerebrospinal fluid of five NiV inoculated animals, with isolation of Streptococcus suis and Enterococcus faecalis. Staphylococcus hyicus was isolated from the skin lesions of the animal with exudative epidermitis. Along with the observed lymphoid depletion in the lymph nodes of all NiV-infected animals, and the demonstrated ability of NiV to infect porcine peripheral blood mononuclear cells in vitro, this finding warrants further investigation into a possible NiV-induced immunosuppression of the swine host.

Henipavirus: A Review of Laboratory Animal Pathology

“…Several investigators have studied NiV infection in pigs. 1,34,49,76,77 Pigs develop severe respiratory disease and encephalitis following NiV subcutaneous inoculation, resembling field infections. There are no reports of field or experimental HeV infections in pigs.…”

“…55 Nasal and oropharyngeal shedding of NiV can be detected 2 to 17 days. 1,78 NiV can be spread from pig to pig by nasal secretions. 49 Virus can be isolated from the serum at 24 days, indicating a slower clearance of virus in some NiV-infected pigs.…”

“…49 Virus can be isolated from the serum at 24 days, indicating a slower clearance of virus in some NiV-infected pigs. 1 Mice. Mice are not a suitable model of NiV disease.…”

Determination of the henipavirus phosphoprotein gene mRNA editing frequencies and detection of the C, V and W proteins of Nipah virus in virus-infected cells

“…With the availability of a full-length NiV reverse genetics system, further investigation of the roles of C, V and W in viral replication and pathogenesis is now possible (Yoneda et al, 2006). A report indicating that NiV can cause immunosuppression in pigs suggests that dissecting the impact of the C, V and W proteins during NiV infection in vivo will be key to understanding the molecular mechanisms of pathogenesis (Berhane et al, 2008). A secondary anti-mouse/rabbit immunoglobulin G conjugated with Alexafluor-488 was used for detection (green) and DAPI was used to stain the nuclei (blue).…”

Animal Challenge Models of Henipavirus Infection and Pathogenesis

“…NiV infection of pigs is frequently asymptomatic, this was especially noted following natural infections but also later during experimental challenge of pigs with NiV by the ocular and oronasal route (Mohd Nor et al 2000;Middleton et al 2002; Human infection and pathogenesis (Chadha et al, 2006;Goh et al, 2000;Hsu et al, 2004;Wong et al, 2002) c HeV-infected guinea pig (Hooper et al, 1997b;Torres-Velez et al, 2008;Westbury et al, 1995;Williamson et al, 2000Williamson et al, , 2001; NiV-infected guinea pig Wong et al, 2003) HeV-infected African green monkey (Bossart et al, 2011;Rockx et al, 2010); NiV-infected African green monkey l NiV-infected squirrel monkey (Marianneau et al, 2010) m HeV-infected horse (Hooper et al, 1997a;Marsh et al, 2011;Murray et al, 1995aMurray et al, , 1995bWilliamson et al, 1998) n Model developed for equine and/or livestock vaccine development Weingartl et al 2006;Berhane et al 2008; also refer to the chapter on Henipaviruses in their natural host (Middleton and Weingartl, this issue). When symptoms were appare...…”