病毒學(xué)雙語版Chapter-2ppt課件

1、Chapter 7: PathogenesisSlide 1/47Pathogenesis90% of cases).Fulminant hepatitis, developing quickly & lasting a short time, causing liver failure & a mortality rate of approximately 90% (1% of cases).Chronic infection, leading to the establishment of a carrier state with virus persistence (ab

2、out 10% of cases).Chapter 7: PathogenesisSlide 29/47HBV & Hepatocellular Carcinoma (HCC)There are approximately 350 million chronic HBV carriers worldwide.The total population of the world is approximately 6 billion, therefore about 5% of the world population is persistently infected with HBV.Al

3、l of these chronic carriers of the virus are at 100-200 times the risk of non-carriers of developing HCC.HCC is a rare tumour in the West, where it represents 2% of fatal cancers.Most cases which do occur in the West are alcohol-related & this is an important clue to the pathogenesis of the tumo

4、ur. However, in South-East Asia & in China, HCC is the most common fatal cancer, causing about half a million deaths every year.The virus might cause the formation of the tumour by three different pathways: direct activation of a cellular oncogene(s), trans-activation of a cellular oncogene(s),

5、or indirectly via tissue regeneration.Chapter 7: PathogenesisSlide 30/47HBV & Hepatocellular Carcinoma (HCC)Macintosh PICTimage formatis not supportedMaci nt osh PI CTi mage f or mati s not suppor t edM a c i n t o s h P I C Ti m a g e f o r m a ti s n o t s u p p o r t e dM acintosh P IC Tim ag

6、e form atis not supportedChapter 7: PathogenesisSlide 31/47HBV & Hepatocellular Carcinoma (HCC)As with EBV & Burkitts lymphoma, the relationship between HBV & HCC is not clear cut:Cirrhosis (a hardening of the liver which may be the result of infections or various toxins, e.g. alcohol) a

7、ppears to be a prerequisite for the development of HCC.It would appear that chronic liver damage induces tissue regeneration & that faulty DNA repair mechanisms result eventually in malignant cell transformation.Unrelated viruses which cause chronic active hepatitis, such as the flavivirus hepat

8、itis C virus (HCV), are also associated with HCC after a long latent period.A number of co-factors, such as aflatoxins & nitrosamines, can induce HCC-like tumours in experimental animals without virus infection. Such substances could also be involved in human HCC.There is no consistent evidence

9、for the integration of the HBV genome or even the persistence of particular HBV genes (e.g. the X gene, which encodes a trans-activator protein functionally analogous to the HTLV tax protein) in tumour cells.Chapter 7: PathogenesisSlide 32/47New & Emergent VirusesThere are numerous examples of s

10、uch viruses which appear to have mysteriously altered their behaviour with time, with significant effects on their pathogenesis.One example of this phenomenon is poliovirus.It is known that poliovirus & poliomyelitis have existed in human populations for at least 4,000 years.For most of this tim

11、e, the pattern of disease was endemic rather than epidemic, i.e. a low, continuous level of infection in particular geographical areas.During the first half the twentieth century, the pattern of occurrence of poliomyelitis in Europe, North America & Australia changed to an epidemic one, with vas

12、t annual outbreaks of infantile paralysis.Although we do not have samples of polioviruses from earlier centuries, the clinical symptoms of the disease give no reason to believe that the virus changed substantially.Why then did the pattern of disease change so dramatically?Chapter 7: PathogenesisSlid

13、e 33/47PoliomyelitisIn rural communities with primitive sanitation facilities, poliovirus circulated freely.Serological surveys in similar contemporary situations reveal that more than 90% of children of 3 years of age have antibodies to at least one of the three serotypes of poliovirus.Even the mos

14、t virulent strains of poliovirus cause 100-200 subclinical infections for each case of paralytic poliomyelitis seen. In such communities, infants experience subclinical immunizing infections while still protected by maternal antibodies - a form of natural vaccination.The relatively few cases of para

15、lysis & death which do occur are likely to be overlooked, especially in view of high infant mortality rates.Chapter 7: PathogenesisSlide 34/47PoliomyelitisDuring the nineteenth century, industrialization & urbanization changed the pattern of poliovirus transmission.Dense urban populations &a

16、mp; increased travelling afforded opportunities for rapid transmission of the virus.In addition, improved sanitation broke the natural pattern of virus transmission.Children were likely to encounter the virus for the first time at a later age & without the protection of maternal antibodies.These

17、 children were at far greater risk when they did eventually become infected & it is believed that these social changes account for the altered pattern of disease.Fortunately, the widespread use of poliovirus vaccines has since brought the situation under control in industrialized countries, &

18、; global eradication of poliovirus is anticipated by 2019.Chapter 7: PathogenesisSlide 35/47New & Emergent VirusesThere are many examples of the epidemic spread of viruses caused by movement of human populations.Measles & smallpox were not known to the ancient Greeks.Both of these viruses ar

19、e maintained by direct person-to-person transmission & have no known alternative hosts.It has been suggested that it was not until human populations in China & the Roman Empire reached a critical density that these viruses were able to propagate in an epidemic pattern & cause recognizabl

20、e outbreaks of disease.Before this time, the few cases that did occur could easily have been overlooked.Chapter 7: PathogenesisSlide 36/47SmallpoxSmallpox reached Europe from the Far East in 710 AD & in the eighteenth century, achieved plague proportions - five reigning European monarchs died fr

21、om smallpox.However, the worst effects occurred when these viruses were transmitted to the New World.Smallpox was (accidentally) transferred to the Americas by Hernando Corts in 1520.In the next two years, 3.5 million Aztecs died from the disease & the Aztec empire was decimated by disease rathe

22、r than conquest.Although not as highly pathogenic as smallpox, epidemics of measles subsequently finished off the Aztec & Inca civilizations.More recently, the first contacts with isolated groups of Eskimos & tribes in New Guinea & South America have had similarly devastating results, al

23、though on a smaller scale.These historical incidents illustrate the way in which a known virus can suddenly cause illness & death on a catastrophic scale following a change in human behaviour.Chapter 7: PathogenesisSlide 37/47Virus Transmission PatternsMeasles & smallpox viruses are transmit

24、ted exclusively from one human host to another.For viruses with more complex cycles of transmission, e.g. those with secondary hosts & insect vectors, control of infection becomes much more difficult.This is particularly true of the families of viruses known collectively as arboviruses (arenavir

25、uses, bunyaviruses, flaviviruses & togaviruses).As human territory has expanded, this has increasingly brought people into contact with the type of environment where these viruses are found - warm, humid, vegetated areas where insect vectors occur in high densities, such as swamps & jungles.

26、In addition to changes in agricultural practices, many emergent virus diseases are zoonoses, i.e. transmitted from animals to humans.This emphasises the importance of the species barrier in preventing transmission of infectious diseases.Chapter 7: PathogenesisSlide 38/47Virus Transmission PatternsM

27、acin to sh P IC Tim ag e fo rm atis n o t su p p o rtedChapter 7: PathogenesisSlide 39/47Dengue FeverDengue fever is also primarily an urban disease of the tropics, transmitted by Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans.Some outbreaks of dengue fever have involv

28、ed more than a million cases with attack rates of up to 90% of the population. There are believed to be over 40 million cases of Dengue virus infection worldwide each year.This disease was first described in 1780 & by 1906 it was known that the virus was transmitted by mosquitoes & the virus

29、 was isolated in 1944.Therefore, this is not a new virus, but the frequency of Dengue virus infection has increased dramatically in the last twenty years due to factors such as:Chapter 7: PathogenesisSlide 40/47Dengue FeverPopulation movements & the intrusion of humans & domestic animals int

30、o new arthropod habitats, particularly tropical forestsDeforestation, with development of new forest-farmland margins & exposure of farmers & domestic animals to new arthropodsIrrigation, especially primitive irrigation systems which are oblivious to arthropod controlUncontrolled urbanizatio

31、n, with vector populations breeding in accumulations of water (tin cans, old tyres, etc.) & sewageIncreased long-distance air travel, with potential for transport of arthropod vectorsIncreased long-distance livestock transportation, with potential for carriage of viruses & arthropods (especi

32、ally ticks)New routing of long-distance bird migration brought about by new man-made water impoundmentsCessation of mosquito control programmes & political upheaval resulting in degraded primary medical servicesChapter 7: PathogenesisSlide 41/47ArbovirusesOf more than 520 arboviruses known, at l

33、east 100 are pathogenic for humans & lots would meet the criteria for emergent viruses.Attempts to control these diseases rely on twin approaches involving both the control of insect vectors responsible for transmission of the virus to humans & the development of vaccines to protect human po

34、pulations.However, both of these approaches present considerable difficulties, both in avoiding environmental damage & understanding virus pathogenesis & developing appropriate vaccines:Rift Valley Fever virus was first isolated from sheep in 1930 but has caused repeated epidemics in sub-Sah

35、aran Africa during the last 20 years, with human infection rates in epidemic areas as high as 35%.This is an epizootic disease, transmitted from sheep to humans by a number of different mosquitoes.The construction of dams which increase mosquito populations, increasing numbers of sheep & the mov

36、ement of sheep & human populations are believed to be responsible for the upsurge.Chapter 7: PathogenesisSlide 42/47West Nile VirusWest Nile virus is a member of the Japanese encephalitis antigenic complex of the genus Flavivirus, family Flaviviridae.All known members of this complex are transmi

37、ssible by mosquitoes & many of them can cause febrile, sometimes fatal, illnesses in humans.West Nile virus was first isolated in the West Nile district of Uganda in 1937 but is the most widespread of the flaviviruses, with geographic distribution including Africa & Eurasia.Unexpectedly, an

38、outbreak of human arboviral encephalitis attributable to a mosquito-transmitted West Nile-like virus occurred in New York, USA, & surrounding states in 2019, resulting (to January 2000) in 50 cases & 7 deaths.In this case, the virus appears to have been transmitted from wild, domestic &

39、exotic birds by Culex mosquitoes (an urban mosquito that flourishes under dry conditions) - a classic pattern of arbovirus transmission.West Nile virus RNA has been detected in overwintering mosquitoes & in birds & the disease is now endemic in the USA.Chapter 7: PathogenesisSlide 43/47Ebola

40、 VirusEbola virus was first described in 1976 & since then has reappeared several times.The extreme pathogenicity of this virus has severely inhibited investigations, most of which have been carried out using molecular biological techniques. However, important unanswered questions remain:Strain

41、variation: Some strains of Ebola virus are highly pathogenic, whereas other strains are not. Relatively non-pathogenic strains have been isolated from monkeys imported into the USA from the Philippines. The molecular basis for these differences is unknown.Natural hosts & distribution: Most human

42、 infections appear to be associated with contact with infected primates. However, extensive ecological surveys in Central Africa have failed to show any evidence that primates (or any of the thousands of animals, plants & invertebrate species examined) are the natural reservoir for infection.Iso

43、lates from Central Africa appear to be highly pathogenic whereas those from the Philippines are apathogenic for humans.Chapter 7: PathogenesisSlide 44/47Emergent Plant VirusesGroup III geminiviruses are transmitted by insect vectors (whiteflies) & their genomes consist of two circular, single-st

44、randed DNA molecules.These viruses cause a great deal of crop damage in plants such as tomatoes, beans, squash, cassava & cotton & their spread may be directly linked to the inadvertent worldwide dissemination of a particular biotype of the whitefly Bemisia tabaci.This vector is an indiscrim

45、inate feeder, encouraging rapid & efficient spread of viruses from indigenous plant species to neighbouring crops.Chapter 7: PathogenesisSlide 45/47Emergent Plant VirusesTomato spotted wilt virus (TSWV) is a Bunyavirus with a very wide plant host range, infecting over 600 different species from

46、70 families.In recent decades, this virus has been a major agricultural pest in Asia, the Americas, Europe & Africa.Its rapid spread has been the result of dissemination of its insect vector (the thrip Frankinellia occidentalis) & diseased plant material.TSWV is the type species of the Tospovirus genus & has a similar morphology & genomic organization to the other bunyaviruses.However, TSWV undergoes propagative transmission & it has been suggested that it may have acquired an extra gene in the M segment via recombination, either from a plant