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1、Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Academic Press,2000.,Chapter 7:Pathogenesis,Slide,*,/43,Pathogenesis,Learning Objectives:,On completing this session,you should be able to:,Explain the concept of pathogenesis in the c

2、ontext of virus infections.,Discuss the molecular basis for virus-induced immunodeficiency(including AIDS)&cell transformation by viruses.,Understand the ways in which virus infection may result in cellular injury.,Academic Press,2000.,Pathogenicity,Pathogenicity,the capacity of one organism to caus

3、e disease in another,is a complex&variable phenomenon.,At the simplest level there is the question,what is disease?An all-embracing definition would be that it is a departure from the normal physiological parameters of an organism.,This could range from a transient&very minor condition such as a sli

4、ghtly elevated temperature or rather subjective feelings of lethargy to chronic pathologic conditions which eventually result in death.,Any of these conditions may result from a large number of internal or external sources.,However,there is rarely one single factor which causes a disease.,Most disea

5、se states are multi-factorial at one level or another.,Academic Press,2000.,Virus Diseases,Two components are involved:,the direct effects of virus replication,the effects of bodily responses to the infection,The course of any virus infection is determined by a delicate&dynamic balance between the h

6、ost&the virus,as is the extent&severity of virus pathogenesis.,In some virus infections,most of the pathologic symptoms observed are attributable not to virus replication,but to the side-effects of the immune response.,Inflammation,fever,headaches&skin rashes are not usually caused by viruses themse

7、lves,but by the cells of the immune system due to the release of potent chemicals such as interferons&interleukins.,In the most extreme cases,none of the pathologic effects of certain diseases are caused directly by the virus,except that its presence stimulates the activation of the immune system.,A

8、cademic Press,2000.,Virus Pathogenesis,Virus pathogenesis is an abnormal&fairly rare situation-t,he majority of virus infections are silent&do not result in outward signs of disease.,It is sometimes said that viruses would disappear if they killed their hosts-this is not necessarily true.,It is poss

9、ible to imagine viruses with a hit-and-run strategy,moving quickly from one dying host to the next&relying on continuing circulation for their survival.,Nevertheless,there is a clear tendency for viruses not to injure their hosts if possible.,Ideally,a virus would not even provoke an immune response

10、 from its host,or at least be able to hide to avoid the effects.,Three major aspects of virus pathogenesis must be considered:direct cell damage resulting from virus replication,damage resulting from immune activation or suppression,&cell transformation caused by viruses.,Academic Press,2000.,Mechan

11、isms of Cellular Injury,Virus infection results in a number of changes which are detectable by visual or biochemical examination of infected cells.,These changes result from the production of virus proteins&nucleic acids,but also from alterations to the biosynthetic capabilities of cells.,Intracellu

12、lar parasitism by viruses sequesters cellular apparatus such as ribosomes&raw materials which would normally be devoted to synthesizing molecules required by the cell.,Eukaryotic cells must carry out constant macromolecular synthesis,whether they are growing&dividing or in a state of quiescence.,Aca

13、demic Press,2000.,Mechanisms of Cellular Injury,A growing cell clearly needs to manufacture more proteins,more nucleic acids&more of all of its myriad components to increase its size before dividing.,The function of all cells is regulated by controlled expression of their genetic information&the sub

14、sequent degradation of the molecules produced.,Such control relies on a delicate&dynamic balance between synthesis&decay which determines the intracellular levels of all the important molecules in the cell.,This is particularly true of the control of the cell cycle,which determines the behaviour of

15、dividing cells.,Academic Press,2000.,Mechanisms of Cellular Injury,A number of common phenotypic changes can be recognized in virus-infected cells.,These changes are often referred to as the cytopathic effects(c.p.e.)of a virus&include:,1)Altered shape,2)Detachment from the substrate,3)Lysis,4)Membr

16、ane fusion,5)Membrane permeability,6)Inclusion bodies,7)Apoptosis,Academic Press,2000.,Shutoff,A number of viruses which cause cell lysis exhibit a phenomenon known as shutoff early in infection.,Shutoff is the sudden&dramatic cessation of most host cell macromolecular synthesis.,In poliovirus-infected cells,this is the result of production of the virus 2A protein.,This molecule is a protease which cleaves the p220 component of eIF-4F,a complex of proteins required for cap-dependent translation