Download PDF
Thromb Haemost 2009; 102(06): 1014-1023
DOI: 10.1160/TH09-05-0310
Theme Issue Article
Schattauer GmbH

Organ- and endotheliotropism of Nipah virus infections in vivo and in vitro

Andrea Maisner
1   Institute of Virology, Philipps University, Marburg, Germany
,
james Neufeld
2   National Centre for Foreign Animal Disease, Winnipeg, Canada
,
Hana Weingartl
2   National Centre for Foreign Animal Disease, Winnipeg, Canada
› Author Affiliations
Further Information

Publication History

Received: 14 May 2009

Accepted after minor revision: 24 August 2009

Publication Date:
30 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Nipah virus (NiV) is a highly pathogenic paramyxovirus that was first isolated in 1999 during an outbreak in Malaysia. In contrast to other paramyxoviruses NiV infects many mammalian species. Because of its zoonotic potential, the high pathogenicity and the lack of therapeutic treatment, NiV was classified as a biosafety level 4 pathogen. In humans NiV causes a severe acute encephalitis whereas in some animal hosts respiratory symptoms are predominantly observed. Despite the differences in the clinical outcome, microvascular endothelial cell damage predominantly underlies the pathological changes in NiV infections in all sus-ceptible host species. NiV generally induces a pronounced vasculitis which is primarily characterised by endothelial cell necrosis and inflammatory cell infiltration. For future developments of specific antiviral therapies or vaccines, a detailed understanding of the molecular basis of NiV pathogenesis is required.This article reviews the current knowledge about natural and experimental infections in different mammals, focusing on the main organ and cell tropism in vivo, and summarises some recent studies in cell culture on the role of ephrin-B2 and -B3 receptors in NiV infection of endothelial cells.

Keywords

Nipah virus - endothelial cells - cell tropism - organ tropism - ephrin-B2
 

  • References

  • 1 Chua KB. et al. Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia. Lancet 1999; 354: 1257-1259.
    CrossrefPubMedGoogle Scholar
  • 2 Chua KB. et al. Nipah virus: a recently emergent deadly paramyxovirus. Science 2000; 288: 1432-1435.
    CrossrefPubMedGoogle Scholar
  • 3 Murray K. et al. A morbillivirus that caused fatal disease in horses and humans. Science 1995; 268: 94-97.
    CrossrefPubMedGoogle Scholar
  • 4 Wang LF. et al. The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae. J Virol 2000; 74: 9972-9979.
    CrossrefPubMedGoogle Scholar
  • 5 Yob JM. et al. Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia. Emerg Infect Dis 2001; 07: 439-441.
    CrossrefPubMedGoogle Scholar
  • 6 Hooper P. et al. Comparative pathology of the diseases caused by Hendra and Nipah viruses. Microbes Infect 2001; 03: 315-322.
    CrossrefPubMedGoogle Scholar
  • 7 Chua KB. et al. Isolation of Nipah virus from Malaysian Island flying-foxes. Microbes Infect 2002; 04: 145-151.
    CrossrefPubMedGoogle Scholar
  • 8 Wong KT. et al. A golden hamster model for human acute Nipah virus infection. Am J Pathol 2003; 163: 2127-2137.
    CrossrefPubMedGoogle Scholar
  • 9 Lo MK, Rota PA. The emergence of Nipah virus, a highly pathogenic paramyxovirus. J Clin Virol 2008; 43: 396-400.
    CrossrefPubMedGoogle Scholar
  • 10 Hsu VP. et al. Nipah virus encephalitis reemergence, Bangladesh. Emerg Infect Dis 2004; 10: 2082-2087.
    CrossrefPubMedGoogle Scholar
  • 11 Chadha MS. et al. Nipah virus-associated encephalitis outbreak, Siliguri, India. Emerg Infect Dis 2006; 12: 235-240.
    CrossrefPubMedGoogle Scholar
  • 12 Gurley ES. et al. Person-to-person transmission of Nipah virus in a Bangladeshi community. Emerg Infect Dis 2007; 13: 1031-1037.
    CrossrefPubMedGoogle Scholar
  • 13 Luby SP. et al. Foodborne transmission of Nipah virus, Bangladesh. Emerg Infect Dis 2006; 12: 1888-1894.
    CrossrefPubMedGoogle Scholar
  • 14 Reynes JM. et al. Nipah virus in Lyle’s flying foxes, Cambodia. Emerg Infect Dis 2005; 11: 1042-1047.
    CrossrefPubMedGoogle Scholar
  • 15 Wacharapluesadee S. et al. Bat Nipah virus, Thailand. Emerg Infect Dis 2005; 11: 1949-1951.
    CrossrefPubMedGoogle Scholar
  • 16 Sendow I. et al. Henipavirus in Pteropus vampyrus bats, Indonesia. Emerg Infect Dis 2006; 12: 711-712.
    CrossrefPubMedGoogle Scholar
  • 17 Lehle C. et al. Henipavirus and Tioman virus antibodies in pteropodid bats, Madagascar. Emerg Infect Dis 2007; 13: 159-161.
    CrossrefPubMedGoogle Scholar
  • 18 ICTV. VIIIth Report of the International Committee on Taxonomy of Viruses. Academic Press; 2005
    Google Scholar
  • 19 Harcourt BH. et al. Molecular characterization of Nipah virus, a newly emergent paramyxovirus. Virology 2000; 271: 334-349.
    CrossrefPubMedGoogle Scholar
  • 20 Bowden TA. et al. Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2. Nat Struct Mol Biol 2008; 15: 567-572.
    CrossrefPubMedGoogle Scholar
  • 21 Xu K. et al. Host cell recognition by the henipaviruses: crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3. Proc Natl Acad Sci U S A 2008; 105: 9953-9958.
    CrossrefPubMedGoogle Scholar
  • 22 Moll M. et al. Ubiquitous activation of the Nipah virus fusion protein does not require a basic amino acid at the cleavage site. J Virol 2004; 78: 9705-9712.
    CrossrefPubMedGoogle Scholar
  • 23 Diederich S. et al. Role of endocytosis and cathepsin-mediated activation in Nipah virus entry. Virology 2008; 375: 391-400.
    CrossrefPubMedGoogle Scholar
  • 24 Diederich S. et al. The nipah virus fusion protein is cleaved within the endosomal compartment. J Biol Chem 2005; 280: 29899-29903.
    CrossrefPubMedGoogle Scholar
  • 25 Pager CT, Dutch RE. Cathepsin L is involved in proteolytic processing of the Hendra virus fusion protein. J Virol 2005; 79: 12714-12720.
    CrossrefPubMedGoogle Scholar
  • 26 Vogt C. et al. Endocytosis of the nipah virus glycoproteins. J Virol 2005; 79: 3865-3872.
    CrossrefPubMedGoogle Scholar
  • 27 Pager CT. et al. A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L. Virology 2006; 346: 251-257.
    CrossrefPubMedGoogle Scholar
  • 28 Middleton DJ. et al. Experimental Nipah virus infection in pigs and cats. J Comp Pathol 2002; 126: 124-136.
    CrossrefPubMedGoogle Scholar
  • 29 Tanimura N. et al. Reactivity of anti-Nipah virus monoclonal antibodies to formalin-fixed, paraffin-embedded lung tissues from experimental Nipah and Hendra virus infections. J Vet Med Sci 2004; 66: 1263-1266.
    CrossrefPubMedGoogle Scholar
  • 30 Weingartl H. et al. Invasion of the central nervous system in a porcine host by nipah virus. J Virol 2005; 79: 7528-7534.
    CrossrefPubMedGoogle Scholar
  • 31 Daniels PW. et al. Infection and disease in reservoir and spillover hosts: determinants of pathogen emergence. Curr Top Microbiol Immunol 2007; 315: 113-131.
    PubMedGoogle Scholar
  • 32 Mungall BA. et al. Vertical transmission and fetal replication of Nipah virus in an experimentally infected cat. J Infect Dis 2007; 196: 812-816.
    CrossrefPubMedGoogle Scholar
  • 33 Mungall BA. et al. Feline model of acute nipah virus infection and protection with a soluble glycoprotein-based subunit vaccine. J Virol 2006; 80: 12293-12302.
    CrossrefPubMedGoogle Scholar
  • 34 Middleton DJ. et al. Experimental Nipah virus infection in pteropid bats (Pteropus poliocephalus). J Comp Pathol 2007; 136: 266-272.
    CrossrefPubMedGoogle Scholar
  • 35 Berhane Y. et al. Bacterial infections in pigs experimentally infected with Nipah virus. Transbound Emerg Dis 2008; 55: 165-174.
    CrossrefPubMedGoogle Scholar
  • 36 Wong KT. et al. Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002; 161: 2153-2167.
    CrossrefPubMedGoogle Scholar
  • 37 Tanimura N. et al. Distribution of viral antigens and development of lesions in chicken embryos inoculated with nipah virus. J Comp Pathol 2006; 135: 74-82.
    CrossrefPubMedGoogle Scholar
  • 38 Weingartl HM. et al. Recombinant nipah virus vaccines protect pigs against challenge. J Virol 2006; 80: 7929-7938.
    CrossrefPubMedGoogle Scholar
  • 39 Wong SC. et al. Late presentation of Nipah virus encephalitis and kinetics of the humoral immune response. J Neurol Neurosurg Psychiatry 2001; 71: 552-554.
    CrossrefPubMedGoogle Scholar
  • 40 Chan KP. et al. A survey of Nipah virus infection among various risk groups in Singapore. Epidemiol Infect 2002; 128: 93-98.
    PubMedGoogle Scholar
  • 41 Tan CT, Tan KS. Nosocomial transmissibility of Nipah virus. J Infect Dis 2001; 184: 1367.
    CrossrefPubMedGoogle Scholar
  • 42 Hossain MJ. et al. Clinical presentation of nipah virus infection in Bangladesh. Clin Infect Dis 2008; 46: 977-984.
    CrossrefPubMedGoogle Scholar
  • 43 Paton NI. et al. Outbreak of Nipah-virus infection among abattoir workers in Singapore. Lancet 1999; 354: 1253-1256.
    CrossrefPubMedGoogle Scholar
  • 44 Goh KJ. et al. Clinical features of Nipah virus encephalitis among pig farmers in Malaysia. N Engl J Med 2000; 342: 1229-1235.
    CrossrefPubMedGoogle Scholar
  • 45 Tan CT. et al. Relapsed and late-onset Nipah encephalitis. Ann Neurol 2002; 51: 703-708.
    CrossrefPubMedGoogle Scholar
  • 46 AbuBakar S. et al. Isolation and molecular identification of Nipah virus from pigs. Emerg Infect Dis 2004; 10: 2228-2230.
    CrossrefPubMedGoogle Scholar
  • 47 Mohd MNNor. et al. Nipah virus infection of pigs in peninsular Malaysia. Rev Sci Tech 2000; 19: 160-165.
    CrossrefPubMedGoogle Scholar
  • 48 Weingartl HM. et al. Animal models of henipavirus infection: a review. Vet J 2009; 181: 211-220.
    CrossrefPubMedGoogle Scholar
  • 49 Bonaparte MI. et al. Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus. Proc Natl Acad Sci U S A 2005; 102: 10652-10657.
    CrossrefPubMedGoogle Scholar
  • 50 Negrete OA. et al. EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus. Nature 2005; 436: 401-405.
    CrossrefPubMedGoogle Scholar
  • 51 Gale NW. et al. Ephrin-B2 selectively marks arterial vessels and neovascularization sites in the adult, with expression in both endothelial and smooth-muscle cells. Dev Biol 2001; 230: 151-160.
    CrossrefPubMedGoogle Scholar
  • 52 Shin D. et al. Expression of ephrinB2 identifies a stable genetic difference between arterial and venous vascular smooth muscle as well as endothelial cells, and marks subsets of microvessels at sites of adult neovascularization. Dev Biol 2001; 230: 139-150.
    CrossrefPubMedGoogle Scholar
  • 53 Augustin HG, Reiss Y. EphB receptors and ephrinB ligands: regulators of vascular assembly and homeostasis. Cell Tissue Res 2003; 314: 25-31.
    CrossrefPubMedGoogle Scholar
  • 54 Palmer A, Klein R. Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function. Genes Dev 2003; 17: 1429-1450.
    CrossrefPubMedGoogle Scholar
  • 55 Poliakov A. et al. Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly. Dev Cell 2004; 07: 465-480.
    CrossrefPubMedGoogle Scholar
  • 56 Negrete OA. et al. Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus. PLoS Pathog 2006; 02: e7.
    CrossrefPubMedGoogle Scholar
  • 57 Negrete OA. et al. Single amino acid changes in the Nipah and Hendra virus attachment glycoproteins distinguish ephrinB2 from ephrinB3 usage. J Virol 2007; 81: 10804-10814.
    CrossrefPubMedGoogle Scholar
  • 58 Bossart KN. et al. Functional studies of host-specific ephrin-B ligands as Henipavirus receptors. Virology 2008; 372: 357-371.
    CrossrefPubMedGoogle Scholar
  • 59 Adams RH. Vascular patterning by Eph receptor tyrosine kinases and ephrins. Semin Cell Dev Biol 2002; 13: 55-60.
    CrossrefPubMedGoogle Scholar
  • 60 Kullander K, Klein R. Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 2002; 03: 475-486.
    CrossrefPubMedGoogle Scholar
  • 61 Makinen T. et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev 2005; 19: 397-410.
    CrossrefPubMedGoogle Scholar
  • 62 Heroult M. et al. Eph receptor and ephrin ligandmediated interactions during angiogenesis and tumor progression. Exp Cell Res 2006; 312: 642-650.
    CrossrefPubMedGoogle Scholar
  • 63 Korff T. et al. Endothelial ephrinB2 is controlled by microenvironmental determinants and associates context-dependently with CD31. Arterioscler Thromb Vasc Biol 2006; 26: 468-474.
    PubMedGoogle Scholar
  • 64 Wang HU. et al. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 1998; 93: 741-753.
    CrossrefPubMedGoogle Scholar
  • 65 Adams RH. et al. The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration. Cell 2001; 104: 57-69.
    CrossrefPubMedGoogle Scholar
  • 66 Zetter BR. Endothelial heterogeneity: Influence of vessel size, organ localization and species specificity on the properties of cultured endothelial cells. In: Ryan USe. editor. Endothelial Cells. 02 Boca Raton, FL: CRC Press; 1988: 63-79.
    Google Scholar
  • 67 Hafner C. et al. Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers. Clin Chem 2004; 50: 490-499.
    CrossrefPubMedGoogle Scholar
  • 68 Rubin LL, Staddon JM. The cell biology of the blood-brain barrier. Annu Rev Neurosci 1999; 22: 11-28.
    CrossrefPubMedGoogle Scholar
  • 69 Imperiali M. et al. O Mannosylation of alpha-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function. J Virol 2005; 79: 14297-14308.
    CrossrefPubMedGoogle Scholar
  • 70 Kullander K. et al. Role of EphA4 and EphrinB3 in local neuronal circuits that control walking. Science 2003; 299: 1889-1892.
    CrossrefPubMedGoogle Scholar
  • 71 Gramberg T. et al. Interactions of LSECtin and DCSIGN/DC-SIGNR with viral ligands: Differential pH dependence, internalization and virion binding. Virology 2008; 373: 189-201.
    CrossrefPubMedGoogle Scholar
  • 72 Simmons G. et al. DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 2003; 305: 115-123.
    CrossrefPubMedGoogle Scholar
  • 73 McFadden G. Poxvirus tropism. Nat Rev Microbiol 2005; 03: 201-213.
    CrossrefPubMedGoogle Scholar
  • 74 Nisole S. et al. TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol 2005; 03: 799-808.
    CrossrefPubMedGoogle Scholar
  • 75 Holmes RK. et al. APOBEC-mediated viral restriction: not simply editing?. Trends Biochem Sci 2007; 32: 118-128.
    CrossrefPubMedGoogle Scholar
  • 76 Sadler AJ, Williams BR. Interferon-inducible antiviral effectors. Nat Rev Immunol 2008; 08: 559-568.
    CrossrefPubMedGoogle Scholar
  • 77 Argyris EG. et al. The interferon-induced expression of APOBEC3G in human blood-brain barrier exerts a potent intrinsic immunity to block HIV-1 entry to central nervous system. Virology 2007; 367: 440-451.
    CrossrefPubMedGoogle Scholar
  • 78 Erbar S. et al. Selective receptor expression restricts Nipah virus infection of endothelial cells. Virol J 2008; 05: 142.
    CrossrefPubMedGoogle Scholar
  • 79 Pasquale EB. Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 2005; 06: 462-475.
    CrossrefPubMedGoogle Scholar
  • 80 Hamada K. et al. Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells. Arterioscler Thromb Vasc Biol 2003; 23: 190-197.
    CrossrefPubMedGoogle Scholar
  • 81 Fuller T. et al. Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells. J Cell Sci 2003; 116: 2461-2470.
    CrossrefPubMedGoogle Scholar
  • 82 Thiel L. et al. Ephrin-B2 expression critically influences Nipah virus infection independent of its cytoplasmic tail. Virol J 2008; 05: 163.
    CrossrefPubMedGoogle Scholar
  • 83 Stins MF. et al. Selective expression of adhesion molecules on human brain microvascular endothelial cells. J Neuroimmunol 1997; 76: 81-90.
    CrossrefPubMedGoogle Scholar
  • 84 Edgell CJ. et al. Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci U S A 1983; 80: 3734-3737.
    CrossrefPubMedGoogle Scholar
  • 85 Kim I. et al. EphB ligand, ephrinB2, suppresses the VEGF-and angiopoietin 1-induced Ras/mitogen-activated protein kinase pathway in venous endothelial cells. Faseb J 2002; 16: 1126-1128.
    CrossrefPubMedGoogle Scholar
  • 86 Parashar UD. et al. Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998-1999 outbreak of severe encephalitis in Malaysia. J Infect Dis 2000; 181: 1755-1759.
    CrossrefPubMedGoogle Scholar
  • 87 Chua KB. Nipah virus outbreak in Malaysia. J Clin Virol 2003; 26: 265-275.
    CrossrefPubMedGoogle Scholar
  • 88 Anonymous. Nipah encephalitis outbreak over a wide area of Bangladesh. Health Sci Bull 2004; 02: 7-11.
    PubMedGoogle Scholar
  • 89 WHO. Nipah virus outbreak(s) in Bangladesh, January-April 2004. Wkly Epidemiol Rec 2004; 17: 168-171.
    PubMedGoogle Scholar
  • 90 Anonymous. Nipah virus outbreak from date palm juice. Health Sci Bull 2005; 03: 1-5.
    PubMedGoogle Scholar
  • 91 Anonymous. Person-to-person transmission of Nipah infection in Bangladesh. Health Sci Bull 2007; 05: 1-6.
    PubMedGoogle Scholar
  • 92 Anonymous. Outbreaks of Nipah virus in Rajbari and Manikgonj. Health Sci Bull 2008; 06: 12-13.
    PubMedGoogle Scholar
  • 93 Bishop KA, Broder CC. Hendra and Nipah Viruses: Lethal Zoonotic Paramyxoviruses. In: Emerging infections. Washington DC: ASM Press; 2008: 155-187.
    Google Scholar