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- Epidemiological Study On Highly Pathogenic Avian Influenza $literal Experimental Study On The Infection And Propagation

Posted on:2008-06-01Degree:MasterType:Thesis
Country:ChinaCandidate:X W DaiFull Text:PDF
GTID:2204360218955897Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Avian influenza is caused by type A influenza virus and occursnaturally among wild birds. Avian influenza virus belongs toOrthomyxoviridae influenza A virus, which can be classified tohemagglutinin and neuraminidase subtype depending on the antigen ofvirus. There are 16 hemagglutinin subtypes and 9 neuraminidase subtypesnow. H5N1, H9N2 and H7N7 subtype can infect human beings, andH5N1 subtype caused the most popular and serious infection. Influenza Aviruses had transmitted to humans from birds in HongKong in 1997.Since then, The viruses have spread to mainland in China, Japan,Cambodia, Laos, Vietnam, Thailand, Indonesia, Egypt, Iraq, Turkey andNigeria. Human H5N1 infections were identified much more in Thailand,Vietnam and Indonesia than other countries. According to the statistics byWorld Health Organization, There are 177 deaths among 298 infectedindividuals by March 2007 with a high mortality of 59.6 percent. Theoutbreaks of H5N1 avian influenza virus infection not only caused largeloss in economy, but also threat our human beings health. It is urgent toprevent and control the spread of avian influenza.The infection and transmission of avian influenza virus are definitein avian species. But we do not know whether it can infect mammalianhost through other approaches besides through nasal cavity or not and whether it can transmit among mammals or among humans or not. Westudied the characteristic of infection and transmission about avianinfluenza virus in BALB/c mice which are very sensitive to H5N1 virus.Firstly BALB/c mice were inoculated with H5N1 virus by feeding onvirus-contaminated feed, douching orally, intraperitoneal injection andwounded skin then examined by etiology, virological and pathologicalassays. Secondly BALB/c mice were inoculated with H5N1 virus throughthe nasal cavity. Then several sentinel mice were placed in the sameenclosure to investigate whether mice could be infected via horizontaltransmission. Although horizontal transmission of avian influenza viruscommonly occurs, proof of vertical transmission is lacking. To clearifywhether H5N1 can vertically transmit or not, We infectedpregnant-14-days BALB/c mice by intranasal to investigate if embryomice could be infected or not.All mice that were inoculated by multiple extra-respiratory approachmanifested significant clinical symptoms. In all mice, the diagnosis ofH5N1 virus was confirmed by means of viral isolation or reversetranscriptase-polymerase chain reaction (RT-PCR) with specific for HA.IgG antibody was detected in the serum 7 days after inoculation.Pathological lesions in lungs, livers, brains and other organs wereobserved. So there are potentially novel ways except respiratory, throughwhich virus could enter mammalian hosts. Moreover, Among 8 sentinel mice, we detected H5N1 virus from 3 mice through etiology assays,suggesting horizontal transmission of avian influenza viruses could occurin mammals. And 1 of 4 embryo mice tissues could isolate H5N1 virus, 3of 4 embryo mice were positive for influenza A virus by RT-PCR.Interestingly, One surviving pregnant mice born infant mice 5 days afterinoculation, 2 of the infant mice survive to 16 days after born. Wedetected high levels of IgG antibody in the serum of the two infant mice,which demonstrates that H5N1 virus could be transmitted verticallythrough placenta.This study in BALB/c mice demonstrates that highly pathogenicityH5N1 virus could infect mammalian hosts by many ways, includingaerosol, fecal-oral, wounded skin, close contact and so on. During thespread of virus, all such factors may be effective. Besides horizontaltransmission, our experiments also reveal that the H5NI viruses can bespread vertically, which may establish the foundation of epidemiologystudy and be meaningfully for preventing and controlling avian influenza.Elsewhere, we can produce H5N1 infectious animal models by all kindsof approach such as alimentary tract, intraperitoneal injection, woundedskin and natural fashion, which may provide insight to the mechanism ofavian influenza virus infection. Last but not the least, in the experimentswe detected high levels of IgG antibody in the serum of the survivinginfant mice after vertically infected. The antibody could neutralize H5N1 viruses efficiently, which may greatly facilitate the production of higherefficient anti-H5N1 serum.
Keywords/Search Tags:avian influenza, H5N1 virus, infection, horizontal transmission, vertical transmission, BALB/c mice
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