Mice (ddY strain, 4 weeks old) were infected intranasally with the H5N1 influenza viruses A/Hong Kong/156/97 (HK156) and A/Hong Kong/483/97 (HK483) isolated from humans. HK156 and HK483 required 200 and 5 p.f.u. of virus, respectively, to give a 50% lethal dose to the mice when the volume of inoculum was set at 10 μl. Both viruses caused encephalitis and severe bronchopneumonia in infected mice. The severity of lung lesions caused by the viruses was essentially similar, whereas HK483 caused more extensive lesions in the brain than did HK156. This was supported by the results of virus titration of organ homogenates, which showed that the virus titres in brains of HK483-infected mice were more than 100-fold higher than those of HK156-infected mice, while those in lungs were almost equivalent. Both viruses were detected in homogenates of the heart, liver, spleen and kidney and blood of the infected mice. Virus antigen was detected by immunohistology in the heart and liver, albeit sporadically, but caused no degenerative change in these organs. The antigen was not detected in the thymus, spleen, pancreas, kidney or gastrointestinal tract. In contrast, virus antigen was found frequently in adipose tissues attached to those organs. The adipose tissues showed severe degenerative change and the virus titres in the tissues were high and comparable to those in lungs. Thus, infection of HK156 and HK483 in our mouse model was pneumo-, neuro- and adipotropic, but not pantropic. Furthermore, HK483 showed higher neurotropism than HK156, which may account for its higher lethality.
BaerG. M.1975; Rabies in nonhematophagous bats. In The Natural History of Rabies pp 79–97 Edited by
BaerG. M.
New York, San Francisco & London: Academic Press;
BenderC.,
HallH.,
HuangJ.,
KlimovA.,
CoxN.,
HayA.,
GregoryV.,
CameronK.,
LimW.,
SubbaraoK.1999; Characteristics of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997–1998. Virology 254:115–123
BruggemanC. A.,
BruningJ. H.,
GraulsG.,
van den BogaardA. E. J. M.,
BosmanF.1987; Presence of cytomegalovirus in brown fat. Study in a rat model. Intervirology 27:32–37
ClaasE. C.,
OsterhausA. D.,
van BeekR.,
De JongJ. C.,
RimmelzwaanG. F.,
SenneD. A.,
KraussS.,
ShortridgeK. F.,
WebsterR. G.1998; Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 351:472–477
DybingJ. K.,
Schultz-CherryS.,
SwayneD. E.,
SuarezD. L.,
PerdueM. L.2000; Distinct pathogenesis of Hong Kong-origin H5N1 viruses in mice compared to that of other highly pathogenic H5 avian influenza viruses. Journal of Virology 74:1443–1450
GaoP.,
WatanabeS.,
ItoT.,
GotoH.,
WellsK.,
McGregorM.,
CooleyA. J.,
KawaokaY.1999; Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong. Journal of Virology 73:3184–3189
GubarevaL. V.,
McCullersJ. A.,
BethellR. C.,
WebsterR. G.1998; Characterization of influenza A/Hong Kong/156/97 (H5N1) virus in a mouse model and protective effect of zanamivir on H5N1 infection in mice. Journal of Infectious Diseases 178:1592–1596
HinshawV.1998; Influenza in other species (seal, whale and mink). In Textbook of Influenza pp 163–167 Edited by
NicholsonK.,
WebsterR. G.,
HayA.
London: Blackwell Science;
IwasakiT.,
TamuraS.,
KumasakaT.,
SatoY.,
HasegawaH.,
AsanumaH.,
AizawaS.,
YanagiharaR.,
KurataT.1999; Exacerbation of influenza virus pneumonia by intranasal administration of surfactant in a mouse model. Archives of Virology 144:675–685
LuX.,
TumpeyT. M.,
MorkenT.,
ZakiS. R.,
CoxN. J.,
KatzJ. M.1999; A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. Journal of Virology 73:5903–5911
MurphyF. A.,
TaylorW. P.,
MimsC. A.,
MarshallI. D.1973; Pathogenesis of Ross River virus infection in mice. II. Muscle, heart, and brown fat lesions. Journal of Infectious Diseases 127:129–138
PriceP.,
EddyK. S.,
PapadimitriouJ. M.,
RobertsonT. A.,
ShellamG. R.1990; Cytomegalovirus infection of adipose tissues induces steatitis in adult mice. International Journal of Experimental Pathology 71:557–571
SuarezD. L.,
PerdueM. L.,
CoxN.,
RoweT.,
BenderC.,
HuangJ.,
SwayneD. E.1998; Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong. Journal of Virology 72:6678–6688
SubbaraoK.,
KlimovA.,
KatzJ.,
RegneryH.,
LimW.,
HallH.,
PerdueM.,
SwayneD.,
BenderC.,
HuangJ.,
HemphillM.,
RoweT.,
ShawM.,
XuX.,
FukudaK.,
CoxN.1998; Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279:393–396
TakadaA.,
KubokiN.,
OkazakiK.,
NinomiyaA.,
TanakaH.,
OsakiH.,
ItamuraS.,
NishimuraH.,
EnamiM.,
TashiroM.,
ShortridgeK. F.,
KidaH.1999; Avirulent avian influenza virus as a vaccine strain against a potential human pandemic. Journal of Virology 73:8303–8307
WebsterR. G.,
GeraciJ.,
PeturssonG.,
SkirnissonK.1981; Conjunctivitis in human beings caused by influenza A virus of seals. New England Journal of Medicine 304:911
YangH. Y.,
JorisI.,
MajnoG.,
WelshR. M.1985; Necrosis of adipose tissue induced by sequential infections with unrelated viruses. American Journal of Pathology 120:173–177
YuenK. Y.,
ChanP. K. S.,
PeirisM.,
TsangD. N. C.,
QueT. L.,
ShortridgeK. F.,
CheungP. T.,
ToW. K.,
HoE. T. F.,
SungR.,
ChengA. F. B. and members of the H5N1 study group; 1998; Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 351:467–471