Experimental Infection of Squirrel Monkeys with Nipah Virus

Marianneau, Philippe; Guillaume, Vanessa; Wong, Kum-Thong; Munisamy, Badmanathan; Looi, R.Y.; Murri, Séverine; Loth, Philippe; Tordo, Noël; Wild, T. F.; Horvat, Branka; Contamin, Hugues

doi:10.3201/eid1603.091346

Cited by 58 publications

(46 citation statements)

References 15 publications

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“…Detailed follow-up of virus dissemination within the host after transfer of virus-loaded leukocytes should allow further analysis of leukocytes in NiV spread. Accordingly, in experimentally infected squirrel monkeys, NiV is also detected only associated with PBMC and is not found in plasma (29). However, occasionally, virus was found in both blood cell and plasma compartments from African green monkeys and cats infected by NiV, although virus detection required RT-PCR with 50 cycles of amplification, suggesting that there was only a very small amount of free virus (18,30).…”

Section: Discussionmentioning

confidence: 99%

Nipah Virus Uses Leukocytes for Efficient Dissemination within a Host

Mathieu

Pohl

Szécsi

et al. 2011

J Virol

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Nipah virus (NiV) is a recently emerged zoonotic paramyxovirus whose natural reservoirs are several species of Pteropus fruit bats. NiV provokes a widespread vasculitis often associated with severe encephalitis, with up to 75% mortality in humans. We have analyzed the pathogenesis of NiV infection, using human leukocyte cultures and the hamster animal model, which closely reproduces human NiV infection. We report that human lymphocytes and monocytes are not permissive for NiV and a low level of virus replication is detected only in dendritic cells. Interestingly, despite the absence of infection, lymphocytes could efficiently bind NiV and transfer infection to endothelial and Vero cells. This lymphocyte-mediated transinfection was inhibited after proteolytic digestion and neutralization by NiV-specific antibodies, suggesting that cells could transfer infectious virus to other permissive cells without the requirement for NiV internalization. In NiV-infected hamsters, leukocytes captured and carried NiV after intraperitoneal infection without themselves being productively infected. Such NiV-loaded mononuclear leukocytes transfer lethal NiV infection into naïve animals, demonstrating efficient virus transinfection in vivo. Altogether, these results reveal a remarkable capacity of NiV to hijack leukocytes as vehicles to transinfect host cells and spread the virus throughout the organism. This mode of virus transmission represents a rapid and potent method of NiV dissemination, which may contribute to its high pathogenicity.

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Section: Discussionmentioning

confidence: 99%

Nipah Virus Uses Leukocytes for Efficient Dissemination within a Host

Mathieu

Pohl

Szécsi

et al. 2011

J Virol

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“…Serological studies indicated that NiV occurred in dogs, cats, horses and goats in the outbreak areas of Malaysia but all were effectively dead-end hosts [84]. Apart from pigs, experimental infection has been produced in cats [64], golden hamsters [94] and squirrel monkeys (Saimiri sciureus) [62]. Experimental studies have shown that infected cats shed NiV through the nasopharynx and in urine during viremic phase and of 2 cats infected, one recovered from experimental NiV infection with a high neutralizing antibody titer within 21 days [64].…”

Section: The Host Rangementioning

confidence: 99%

Nipah virus infection: current scenario

et al. 2013

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“…Endogenous peroxidase was blocked with 0.6% H 2 O 2 in methanol for 20 min. The primary antibody was a mouse polyclonal, cross-reacting, anti-Hendra virus antibody used at a 1:2,000 dilution (38,61). Positive signals were revealed by linking secondary antimouse antibodies and diaminobenzidine as the substrate.…”

Section: Methodsmentioning

confidence: 99%

Nonstructural Nipah Virus C Protein Regulates both the Early Host Proinflammatory Response and Viral Virulence

Mathieu

Guillaume

Volchkova

et al. 2012

J Virol

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Nipah virus (NiV) is a highly pathogenic, negative-strand RNA paramyxovirus that has recently emerged from flying foxes to cause serious human disease. We have analyzed the role of the nonstructural NiV C protein in viral immunopathogenesis using recombinant virus lacking the expression of NiV C (NiVΔC). While wild-type NiV was highly pathogenic in the hamster animal model, NiVΔC was strongly attenuated. Replication of NiVΔC was followed by the production of NiV-specific antibodies and associated with higher recruitment of inflammatory cells and less intensive histopathological lesions in different organs than in wild-type-NiV-infected animals. To analyze the molecular basis of NiVΔC attenuation, we studied early changes in gene expression in infected primary human endothelial cells, a major cellular target of NiV infection. The transcriptomic approach revealed the striking difference between wild-type and mutant NiV in the expression of genes involved in immunity, with the particularly interesting differential patterns of proinflammatory cytokines. Compared to wild-type virus, NiVΔC induced increased expression of interleukin 1 beta (IL-1β), IL-8, CXCL2, CXCL3, CXCL6, CCL20, and beta interferon. Furthermore, the expression of NiV C in stably transfected cells decreased the production of the same panel of cytokines, revealing a role of the C protein in the regulation of cytokine balance. Together, these results suggest that NiV C regulates expression of proinflammatory cytokines, therefore providing a signal responsible for the coordination of leukocyte recruitment and the chemokine-induced immune response and controlling the lethal outcome of the infection.

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Experimental Infection of Squirrel Monkeys with Nipah Virus

Cited by 58 publications

References 15 publications

Nipah Virus Uses Leukocytes for Efficient Dissemination within a Host

Nipah Virus Uses Leukocytes for Efficient Dissemination within a Host

Nipah virus infection: current scenario

Nonstructural Nipah Virus C Protein Regulates both the Early Host Proinflammatory Response and Viral Virulence

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