The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.
References
[1]
Eaton, B.T.; Broder, C.C.; Middleton, D.; Wang, L.-F. Hendra and Nipah Viruses: different and dangerous. Nat. Rev. Micro. 2006, 4, 23–35, doi:10.1038/nrmicro1323.
[2]
Marsh, G.A.; Wang, L.-F. Hendra and Nipah viruses: Why are they so deadly? Curr. Opin. Virol. 2012, 2, 242–247, doi:10.1016/j.coviro.2012.03.006.
[3]
Field, H.; Kung, N. Henipaviruses — unanswered questions of lethal zoonoses. Curr. Opin. Virol. 2011, 1, 658–661, doi:10.1016/j.coviro.2011.10.025.
[4]
Marsh, G.A.; De Jong, C.; Barr, J.A.; Tachedjian, M.; Smith, C.; Middleton, D.; Yu, M.; Todd, S.; Foord, A.J.; Haring, V.; et al. Cedar virus: A novel henipavirus isolated from australian bats. PLoS Pathogens 2012, 8, e1002836, doi:10.1371/journal.ppat.1002836.
[5]
Murray, K.; Rogers, R.; Selvey, L.; Selleck, P.; Hyatt, A.; Gould, A.; Gleeson, L.; Hooper, P.; Westbury, H. A novel morbillivirus pneumonia of horses and its transmission to humans. Emerg. Infect. Dis. 1995, 1, 31–33, doi:10.3201/eid0101.950107.
Middleton, D.J.; Morrissy, C.J.; Van der Heide, B.M.; Russell, G.M.; Braun, M.A.; Westbury, H.A.; Halpin, K.; Daniels, P.W. Experimental Nipah virus infection in pteropid bats (Pteropus poliocephalus). J. Comp. Pathol. 2007, 136, 266–272, doi:10.1016/j.jcpa.2007.03.002.
[18]
Williamson, M.; Hooper, P.; Selleck, P.; Gleeson, L.; Daniels, P.; Westbury, H.; Murray, P. Transmission studies of Hendra virus (equine morbilli-virus) in fruit bats, horses and cats. Aust. Vet. J. 1998, 76, 813–818, doi:10.1111/j.1751-0813.1998.tb12335.x.
[19]
Halpin, K.; Hyatt, A.D.; Fogarty, R.; Middleton, D.; Bingham, J.; Epstein, J.H.; Rahman, S.A.; Hughes, T.; Smith, C.; Field, H.E.; Daszak, P. Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a comprehensive experimental study of virus transmission. Am. J. Trop. Med. Hyg. 2011, 85, 946–951, doi:10.4269/ajtmh.2011.10-0567.
[20]
Mohd Nor, M.N.; Gan, C.H.; Ong, B.L. Nipah virus infection of pigs in peninsular Malaysia. Rev. Off. Int. Epizoot. 2000, 19, 160–165.
[21]
Middleton, D.J.; Westbury, H.A.; Morrissy, C.J.; Van der Heide, B.M.; Russell, G.M.; Braun, M.A.; Hyatt, A.D. Experimental Nipah virus infection in pigs and cats. J. Comp. Pathol. 2002, 126, 124–136, doi:10.1053/jcpa.2001.0532.
[22]
22 Weingartl, H.M.; Berhane, Y.; Caswell, J.L.; Loosmore, S.; Audonnet, J.-C.; Roth, J.A.; Czub, M. Recombinant Nipah virus vaccines protect pigs against challenge. J. Virol. 2006, 80, 7929–7938.
[23]
Weingartl, H.; Czub, S.; Copps, J.; Berhane, Y.; Middleton, D.; Marszal, P.; Gren, J.; Smith, G.; Ganske, S.; Manning, L.; Czub, M. Invasion of the Central Nervous System in a Porcine Host by Nipah Virus. J. Virol. 2005, 79, 7528–7534, doi:10.1128/JVI.79.12.7528-7534.2005.
[24]
Berhane, Y.; Weingartl, H.M.; Lopez, J.; Neufeld, J.; Czub, S.; Embury-Hyatt, C.; Goolia, M.; Copps, J.; Czub, M. Bacterial infections in pigs experimentally infected with Nipah virus. Transbound. Emerg. Dis. 2008, 55, 165–174, doi:10.1111/j.1865-1682.2008.01021.x.
[25]
Li, M.; Embury-Hyatt, C.; Weingartl, H.M. Experimental inoculation study indicates swine as a potential host for Hendra virus. Vet. Res. 2010, 41, 33, doi:10.1051/vetres/2010005.
[26]
Hooper, P.; Zaki, S.; Daniels, P.; Middleton, D. Comparative pathology of the diseases caused by Hendra and Nipah viruses. Microbes Infect. 2001, 3, 315–322, doi:10.1016/S1286-4579(01)01385-5.
Rogers, R.J.; Douglas, I.C.; Baldock, F.C.; Glanville, R.J.; Seppanen, K.T.; Gleeson, L.J.; Selleck, P.N.; Dunn, K.J. Investigation of a second focus of equine morbillivirus infection in coastal Queensland. Aust. Vet. J. 1996, 74, 243–244, doi:10.1111/j.1751-0813.1996.tb15413.x.
[29]
Mungall, B.A.; Middleton, D.; Crameri, G.; Bingham, J.; Halpin, K.; Russell, G.; Green, D.; McEachern, J.; Pritchard, L.I.; Eaton, B.T.; et al. Feline model of acute nipah virus infection and protection with a soluble glycoprotein-based subunit vaccine. J. Virol. 2006, 80, 12293–12302.
[30]
Mungall, B.A.; Middleton, D.; Crameri, G.; Halpin, K.; Bingham, J.; Eaton, B.T.; Broder, C.C. Vertical transmission and fetal replication of nipah virus in an experimentally infected cat. J. Infect. Dis. 2007, 196, 812–816, doi:10.1086/520818.
[31]
McEachern, J.A.; Bingham, J.; Crameri, G.; Green, D.J.; Hancock, T.J.; Middleton, D.; Feng, Y.-R.; Broder, C.C.; Wang, L.-F.; et al. A recombinant subunit vaccine formulation protects against lethal Nipah virus challenge in cats. Vaccine 2008, 26, 3842–3852, doi:10.1016/j.vaccine.2008.05.016.
[32]
Westbury, H.A.; Hooper, P.T.; Selleck, P.W.; Murray, P.K. Equine morbillivirus pneumonia: susceptibility of laboratory animals to the virus. Aust. Vet. J. 1995, 72, 278–279.
[33]
Westbury, H.A.; Hooper, P.T.; Brouwer, S.L.; Selleck, P.W. Susceptibility of cats to equine morbillivirus. Aust. Vet. J. 1996, 74, 132–134, doi:10.1111/j.1751-0813.1996.tb14813.x.
[34]
Hooper, P.T.; Westbury, H.A.; Russell, G.M. The lesions of experimental equine morbillivirus disease in cats and guinea pigs. Vet. Pathol. 1997, 34, 323–329, doi:10.1177/030098589703400408.
[35]
Clayton, B.A.; Middleton, D.; Bergfeld, J.; Haining, J.; Arkinstall, R.; Wang, L.; Marsh, G.A. Transmission routes for nipah virus from Malaysia and Bangladesh. Emerg. Infect. Dis. 2012, 18, 1983–1993, doi:10.3201/eid1812.120875.
[36]
Bossart, K.N.; Bingham, J.; Middleton, D. Targeted Strategies for Henipavirus Therapeutics. Open Virol. J. 2007, 1, 14–25.
[37]
Pallister, J.; Middleton, D.; Crameri, G.; Yamada, M.; Klein, R.; Hancock, T.J.; Foord, A.; Shiell, B.; Michalski, W.; Broder, C.C.; et al. Chloroquine administration does not prevent nipah virus infection and disease in ferrets. J. Virol. 2009, 83, 11979–11982, doi:10.1128/JVI.01847-09.
[38]
Bossart, K.N.; Zhu, Z.; Middleton, D.; Klippel, J.; Crameri, G.; Bingham, J.; McEachern, J.A.; Green, D.; Hancock, T.J.; Chan, Y.-P.; et al. A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection. PLoS Pathog. 2009, 5, e1000642, doi:10.1371/journal.ppat.1000642.
[39]
Pallister, J.; Middleton, D.; Wang, L.-F.; Klein, R.; Haining, J.; Robinson, R.; Yamada, M.; White, J.; Payne, J.; Feng, Y.-R.; et al. A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge. Vaccine 2011, 29, 5623–5630, doi:10.1016/j.vaccine.2011.06.015.
[40]
Marianneau, P. Experimental infection of squirrel monkeys with Nipah virus. Emerg. Infect. Dis. 2010, 16.
[41]
Geisbert, T.W.; Daddario-DiCaprio, K.M.; Hickey, A.C.; Smith, M.A.; Chan, Y.-P.; Wang, L.-F.; Mattapallil, J.J.; Geisbert, J.B.; Bossart, K.N.; Broder, C.C. Development of an Acute and Highly Pathogenic Nonhuman Primate Model of Nipah Virus Infection. PLoS One 2010, 5, e10690, doi:10.1371/journal.pone.0010690.
[42]
Bossart, K.N.; Rockx, B.; Feldmann, F.; Brining, D.; Scott, D.; Lacasse, R.; Geisbert, J.B.; Feng, Y.-R.; Chan, Y.-P.; Hickey, A.C.; et al. A hendra virus g glycoprotein subunit vaccine protects african green monkeys from nipah virus challenge. Sci. Transl. Med. 2012, 4, 46ra107, doi:10.1126/scitranslmed.3004241.
[43]
Rockx, B.; Bossart, K.N.; Feldmann, F.; Geisbert, J.B.; Hickey, A.C.; Brining, D.; Callison, J.; Safronetz, D.; Marzi, A.; Kercher, L.; et al. A novel model of lethal hendra virus infection in african green monkeys and the effectiveness of ribavirin treatment. J. Virol. 2010, 84, 9831–9839, doi:10.1128/JVI.01163-10.
[44]
Bossart, K.N.; Geisbert, T.W.; Feldmann, H.; Zhu, Z.; Feldmann, F.; Geisbert, J.B.; Yan, L.; Feng, Y.-R.; Brining, D.; et al. A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge. Sci. Transl. Med. 2011, 3, 105ra103, doi:10.1126/scitranslmed.3002901.
[45]
Dhondt, K.P.; Mathieu, C.; Chalons, M.; Reynaud, J.M.; Vallve, A.; Raoul, H.; Horvat, B. Type I interferon signaling protects mice from lethal Henipavirus infection. J. Infect. Dis. 2012, 207, 142–151.
[46]
Dups, J.; Middleton, D.; Yamada, M.; Monaghan, P.; Long, F.; Robinson, R.; Marsh, G.A.; Wang, L.-F. A new model for hendra virus encephalitis in the mouse. PLoS One 2012, 7, e40308.
[47]
Wong, K.T.; Grosjean, I.; Brisson, C.; Blanquier, B.; Fevre-Montange, M.; Bernard, A.; Loth, P.; Georges-Courbot, M.-C.; Chevallier, M.; Akaoka, H.; et al. A golden hamster model for human acute Nipah virus infection. Am. J. Pathol. 2003, 163, 2127–2137, doi:10.1016/S0002-9440(10)63569-9.
[48]
Rockx, B.; Brining, D.; Kramer, J.; Callison, J.; Ebihara, H.; Mansfield, K.; Feldmann, H. Clinical outcome of henipavirus infection in hamsters is determined by the route and dose of infection. J. Virol. 2011, 85, 7658–7671, doi:10.1128/JVI.00473-11.
[49]
De Wit, E.; Bushmaker, T.; Scott, D.; Feldmann, H.; Munster, V.J. Nipah virus transmission in a hamster model. PLoS Negl. Trop. Dis. 2011, 5, e1432, doi:10.1371/journal.pntd.0001432.
[50]
Debuysscher, B.L.; De Wit, E.; Munster, V.J.; Scott, D.; Feldmann, H.; Prescott, J. Comparison of the pathogenicity of nipah virus isolates from bangladesh and malaysia in the Syrian hamster. PLoS Negl. Trop. Dis. 2013, 7, e2024, doi:10.1371/journal.pntd.0002024.
[51]
Yoneda, M.; Guillaume, V.; Sato, H.; Fujita, K.; Georges-Courbot, M.-C.; Ikeda, F.; Omi, M.; Muto-Terao, Y.; Wild, T.F.; Kai, C. The Nonstructural proteins of nipah virus play a key role in pathogenicity in experimentally infected animals. PLoS One 2010, 5, e12709, doi:10.1371/journal.pone.0012709.
[52]
Mathieu, C.; Guillaume, V.; Volchkova, V.A.; Pohl, C.; Jacquot, F.; Looi, R.Y.; Wong, K.T.; Legras-Lachuer, C.; Volchkov, V.E.; Lachuer, J.; et al. Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence. J. Virol. 2012. In Press.
[53]
Mathieu, C.; Guillaume, V.; Sabine, A.; Ong, K.C.; Wong, K.T.; Legras-Lachuer, C.; Horvat, B. Lethal Nipah virus infection induces rapid overexpression of CXCL10. PLoS One 2012, 7, e32157.
[54]
Guillaume, V.; Contamin, H.; Loth, P.; Georges-Courbot, M.-C.; Lefeuvre, A.; Marianneau, P.; Chua, K.B.; Lam, S.K.; Buckland, R.; Deubel, V.; et al. Nipah virus: Vaccination and passive protection studies in a hamster model. J. Virol. 2004, 78, 834–840, doi:10.1128/JVI.78.2.834-840.2004.
[55]
Guillaume, V.; Contamin, H.; Loth, P.; Grosjean, I.; Georges-Courbot, M.C.; Deubel, V.; Buckland, R.; Wild, T.F. Antibody prophylaxis and therapy against Nipah virus infection in hamsters. J. Virol. 2006, 80, 1972–1978, doi:10.1128/JVI.80.4.1972-1978.2006.
[56]
Freiberg, A.N.; Worthy, M.N.; Lee, B.; Holbrook, M.R. Combined chloroquine and ribavirin treatment does not prevent death in a hamster model of Nipah and Hendra virus infection. J. Gen. Virol. 2010, 91, 765–772, doi:10.1099/vir.0.017269-0.
[57]
Georges-Courbot, M.C.; Contamin, H.; Faure, C.; Loth, P.; Baize, S.; Leyssen, P.; Neyts, J.; Deubel, V. Poly(I)-poly(C12U) but not ribavirin prevents death in a hamster model of Nipah virus infection. Antimicrob. Agents Chemother. 2006, 50, 1768–1772, doi:10.1128/AAC.50.5.1768-1772.2006.
[58]
Ploquin, A.; Szécsi, J.; Mathieu, C.; Guillaume, V.; Barateau, V.; Ong, K.C.; Wong, K.T.; Cosset, F.-L.; Horvat, B.; Salvetti, A. Protection against henipavirus infection by use of recombinant adeno-associated virus-vector vaccines. J. Infect. Dis. 2013, 207, 469–478, doi:10.1093/infdis/jis699.
[59]
Guillaume, V.; Wong, K.T.; Looi, R.Y.; Georges-Courbot, M.-C.; Barrot, L.; Buckland, R.; Wild, T.F.; Horvat, B. Acute Hendra virus infection: Analysis of the pathogenesis and passive antibody protection in the hamster model. Virology 2009, 387, 459–465, doi:10.1016/j.virol.2009.03.001.
[60]
Williamson, M.M.; Hooper, P.T.; Selleck, P.W.; Westbury, H.A.; Slocombe, R.F.S. A guinea-pig model of hendra virus encephalitis. J. Comp. Pathol. 2001, 124, 273–279, doi:10.1053/jcpa.2001.0464.
[61]
Williamson, M.M.; Hooper, P.T.; Selleck, P.W.; Westbury, H.A.; Slocombe, R.F. Experimental hendra virus infectionin pregnant guinea-pigs and fruit Bats (Pteropus poliocephalus). J. Comp. Pathol. 2000, 122, 201–207, doi:10.1053/jcpa.1999.0364.
[62]
Calisher, C.H.; Childs, J.E.; Field, H.E.; Holmes, K.V.; Schountz, T. Bats: Important reservoir hosts of emerging viruses. Clin. Microbiol. Rev. 2006, 19, 531–545, doi:10.1128/CMR.00017-06.
[63]
Wong, S.; Lau, S.; Woo, P.; Yuen, K.-Y. Bats as a continuing source of emerging infections in humans. Rev. Med. Virol. 2007, 17, 67–91, doi:10.1002/rmv.520.
[64]
Young, P.L.; Halpin, K.; Selleck, P.W.; Field, H.; Gravel, J.L.; Kelly, M.A.; Mackenzie, J.S. Serologic evidence for the presence in Pteropus bats of a paramyxovirus related to equine morbillivirus. Emerg. Infect. Dis. 1996, 2, 239–240, doi:10.3201/eid0203.960315.
[65]
Halpin, K.; Young, P.L.; Field, H.E.; Mackenzie, J.S. Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus. J. Comp. Pathol. 2000, 81, 1927–1932.
[66]
Yob, J.M.; Field, H.; Rashdi, A.M.; Morrissy, C.; Van der Heide, B.; Rota, P.; Bin Adzhar, A.; White, J.; Daniels, P.; Jamaluddin, A.; et al. Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia. Emerg. Infect. Dis. 2001, 7, 439–441.
[67]
Yadav, P.D.; Raut, C.G.; Shete, A.M.; Mishra, A.C.; Towner, J.S.; Nichol, S.T.; Mourya, D.T. Detection of Nipah virus RNA in fruit bat (Pteropus giganteus) from India. Am. J. Trop. Med. Hyg. 2012, 87, 576–578, doi:10.4269/ajtmh.2012.11-0416.
[68]
Olson, J.G.; Rupprecht, C.; Rollin, P.E.; An, U.S.; Niezgoda, M.; Clemins, T.; Walston, J.; Ksiazek, T.G. Antibodies to Nipah-like virus in bats (Pteropus lylei), Cambodia. Emerg. Infect. Dis. 2002, 8, 987–988, doi:10.3201/eid0809.010515.
Sendow, I.; Field, H.E.; Curran, J.; Darminto; Morrissy, C.; Meehan, G.; Buick, T.; Daniels, P. Henipavirus in Pteropus vampyrus bats, Indonesia. Emerg. Infect. Dis. 2006, 12, 711–712, doi:10.3201/eid1204.051181.
[71]
Wacharapluesadee, S.; Boongird, K.; Wanghongsa, S.; Ratanasetyuth, N.; Supavonwong, P.; Saengsen, D.; Gongal, G.N.; Hemachudha, T. A longitudinal study of the prevalence of Nipah virus in Pteropus lylei bats in Thailand: evidence for seasonal preference in disease transmission. Vector Borne Zoonotic Dis. 2010, 10, 183–190, doi:10.1089/vbz.2008.0105.
[72]
Li, Y.; Wang, J.; Hickey, A.C.; Zhang, Y.; Li, Y.; Wu, Y.; Zhang, H.; Yuan, J.; Han, Z.; McEachern, J.; et al. Antibodies to Nipah or Nipah-like viruses in bats, China. Emerg. Infect. Dis. 2008, 14, 1974–1976, doi:10.3201/eid1412.080359.
[73]
Clayton, B.A.; Wang, L.F.; Marsh, G.A. Henipaviruses: an updated review focusing on the pteropid reservoir and features of transmission. Zoonoses Public Health 2013, 60, 69–83, doi:10.1111/j.1863-2378.2012.01501.x.
Sohayati, A.R.; Hassan, L.; Sharifah, S.H.; Lazarus, K.; Zaini, C.M.; Epstein, J.H.; Shamsyul Naim, N.; Field, H.E.; Arshad, S.S.; Abdul Aziz, J.; et al. Evidence for Nipah virus recrudescence and serological patterns of captive Pteropus vampyrus. Epidemiol. Infect. 2011, 1–10.
[76]
Bossart, K. Functional studies of host-specific ephrin-B ligands as Henipavirus receptors. Virology 2008, 372, 357–371, doi:10.1016/j.virol.2007.11.011.
[77]
Negrete, O.A.; Chu, D.; Aguilar, H.C.; Lee, B. Single amino acid changes in the nipah and hendra virus attachment glycoproteins distinguish EphrinB2 from EphrinB3 usage. J. Virol. 2007, 81, 10804–10814, doi:10.1128/JVI.00999-07.
[78]
Field, H.; Young, P.; Yob, J.M.; Mills, J.; Hall, L.; Mackenzie, J. The natural history of Hendra and Nipah viruses. Microbes Infect. 2001, 3, 307–314, doi:10.1016/S1286-4579(01)01384-3.
[79]
Chua, K.B. Nipah virus outbreak in Malaysia. J. Clin. Virol. 2003, 26, 265–275, doi:10.1016/S1386-6532(02)00268-8.
[80]
Epstein, J.H.; Abdul Rahman, S.; Zambriski, J.A.; Halpin, K.; Meehan, G.; Jamaluddin, A.A.; Hassan, S.S.; Field, H.E.; Hyatt, A.D.; Daszak, P. Feral cats and risk for Nipah virus transmission. Emerg. Infect. Dis. 2006, 12, 1178–1179, doi:10.3201/eid1207.050799.
[81]
Mills, J.N.; Alim, A.N. M.; Bunning, M.L.; Lee, O.B.; Wagoner, K.D.; Amman, B.R.; Stockton, P.C.; Ksiazek, T.G. Nipah virus infection in dogs, Malaysia, 1999. Emerg. Infect. Dis. 2009, 15, 950–952, doi:10.3201/eid1506.080453.
[82]
Hendra virus, equine - Australia (21): (QL) canine. ProMed Mail, 2011. Archive Number: 20110802.2324. Available online: http://www.promedmail.org/ (access on 4 April 2013).
[83]
Hayman, D.T.S.; Wang, L.-F.; Barr, J.; Baker, K.S.; Suu-Ire, R.; Broder, C.C.; Cunningham, A.A.; Wood, J.L.N. Antibodies to henipavirus or henipa-like viruses in domestic pigs in ghana, west Africa. PLoS One 2011, 6, e25256, doi:10.1371/journal.pone.0025256.
[84]
Mathieu, C.; Pohl, C.; Szecsi, J.; Trajkovic-Bodennec, S.; Devergnas, S.; Raoul, H.; Cosset, F.-L.; Gerlier, D.; Wild, T.F.; Horvat, B. Nipah Virus uses leukocytes for efficient dissemination within a host. J. Virol. 2011, 18.
[85]
Stachowiak, B.; Weingartl, H.M. Nipah virus infects specific subsets of porcine peripheral blood mononuclear cells. PLoS One 2012, 7, e30855, doi:10.1371/journal.pone.0030855.
Parashar, U.D.; Sunn, L.M.; Ong, F.; Mounts, A.W.; Arif, M.T.; Ksiazek, T.G.; Kamaluddin, M.A.; Mustafa, A.N.; Kaur, H.; Ding, L.M.; 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, doi:10.1086/315457.
[89]
Munster, V.J.; Prescott, J.B.; Bushmaker, T.; Long, D.; Rosenke, R.; Thomas, T.; Scott, D.; Fischer, E.R.; Feldmann, H.; Wit, E. de Rapid Nipah virus entry into the central nervous system of hamsters via the olfactory route. Sci. Rep. 2012, 2, 736.
[90]
Lo, M.K.; Miller, D.; Aljofan, M.; Mungall, B.A.; Rollin, P.E.; Bellini, W.J.; Rota, P.A. Characterization of the antiviral and inflammatory responses against Nipah virus in endothelial cells and neurons. Virology 2010, 404, 78–88, doi:10.1016/j.virol.2010.05.005.
[91]
Torres-Velez, F.J.; Shieh, W.-J.; Rollin, P.E.; Morken, T.; Brown, C.; Ksiazek, T.G.; Zaki, S.R. Histopathologic and immunohistochemical characterization of Nipah virus infection in the guinea pig. Vet. Pathol 2008, 45, 576–585, doi:10.1354/vp.45-4-576.
[92]
Blackman, M.A.; Woodland, D.L. The narrowing of the CD8 T cell repertoire in old age. Curr. Opin. Immunol. 2011, 23, 537–542, doi:10.1016/j.coi.2011.05.005.
[93]
Frasca, D.; Blomberg, B.B. Aging impairs murine B cell differentiation and function in primary and secondary lymphoid tissues. Aging Dis. 2011, 2, 361–373.
[94]
Kovacs, E.J.; Palmer, J.L.; Fortin, C.F.; Fül？p, T., Jr; Goldstein, D.R.; Linton, P.-J. Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors. Trends Immunol. 2009, 30, 319–324, doi:10.1016/j.it.2009.03.012.
[95]
Müller, U.; Steinhoff, U.; Reis, L.F.; Hemmi, S.; Pavlovic, J.; Zinkernagel, R.M.; Aguet, M. Functional role of type I and type II interferons in antiviral defense. Science 1994, 264, 1918–1921.
