High mortality in Nipah encephalitis is associated with presence of virus in cerebrospinal fluid

Chua, Kaw Bing; Lam, Sai Kit; Tan, Chong Tin; Hooi, Poh Sim; Goh, Khean Jin; Chew, Nee Kong; Tan, Kay Sin; Kamarulzaman, Adeeba; Wong, Kum Thong

doi:10.1002/1531-8249(200011)48:5<802::aid-ana17>3.0.co;2-m

Cited by 71 publications

(31 citation statements)

References 13 publications

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“…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). In humans, NiV has been isolated from urine and cerebrospinal fluid from infected patients (12,13,43), but there is no report of isolation from serum. Thus, PBMC appear much more appropriate than serum for NiV diagnosis and virus isolation from infected patients.…”

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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“…The main target cells during the late stage of henipavirus infection in humans are endothelial cells of blood vessels, resulting in vasculitis, vasculitis-induced thrombosis, and vascular microinfarction in the central nervous system (CNS) but also in other organs such as the lungs, spleen, and kidneys (27)(28)(29). The infection also reaches the CNS parenchymal cells, which all together play an important role in the pathogenicity of henipaviruses (27,30).…”

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confidence: 99%

“…The infection also reaches the CNS parenchymal cells, which all together play an important role in the pathogenicity of henipaviruses (27,30).…”

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confidence: 99%

Henipavirus Pathogenesis in Human Respiratory Epithelial Cells

Escaffre

Borisevich

Carmical

et al. 2013

J Virol

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“…Subsequent outbreaks of NiV occurred in India and almost annually in Bangladesh (6,32,53). The large Malaysian outbreak was marked by severe, fatal encephalitis, with about 40% mortality (11), whereas the smaller, more recent Bangladeshi and Indian outbreaks displayed higher mortality rates (75 to 92%), potential human-to-human transmission, and an increased occurrence of severe respiratory disease (6,23,31). In addition to its high lethality, NiV exhibits a broad host range and is able to infect bats, pigs, humans, cats, dogs, and other species (9,10,46), probably due to the use of highly conserved ephrin B2 and B3 receptors (3).…”

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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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High mortality in Nipah encephalitis is associated with presence of virus in cerebrospinal fluid

Cited by 71 publications

References 13 publications

Nipah Virus Uses Leukocytes for Efficient Dissemination within a Host

Nipah Virus Uses Leukocytes for Efficient Dissemination within a Host

Henipavirus Pathogenesis in Human Respiratory Epithelial Cells

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

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