病毒学双语版课件Cha

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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 6:Infection,Slide,*,/38,Infection:Part 2,Part 1,Academic Press,2000.,Evasion of Immune Responses by Viruses,Inhibition of MHC I-Restricted Antigen Presenta

2、tion:,CTLs can only respond to foreign antigens presented by MHC I complexes on the target cell.,A number of viruses interfere with MHC I expression or function to disrupt this process&evade the CTL response.,Such mechanisms include downregulation of MHC I expression by adenoviruses&interference wit

3、h the antigen processing required to form an MHC I-antigen complex by herpesviruses.,Academic Press,2000.,Evasion of Immune Responses by Viruses,Inhibition of MHC II Restricted-Antigen Presentation:,MHC-II antigens are essential in the adaptive immune response in order to stimulate the development o

4、f antigen-responsive clones of effector cells.,Herpesviruses&papillomaviruses interfere with the processing&surface expression of MHC II-antigen complexes,inhibiting the CTL response.,Inhibition of Natural Killer Cell Lysis:,The poxvirus,Molluscum contagiosum,encodes a homologue of MHC I which is ex

5、pressed on the surface of infected cells but is unable to bind an antigenic peptide,thus avoiding killing by NK cells which would be triggered by the absence of MHC I on the cell surface.,Similar proteins are made by other viruses such as HHV-5(CMV),&herpesviruses in general appear to have a number

6、of sophisticated mechanisms to avoid NK cell killing.,Academic Press,2000.,Evasion of Immune Responses by Viruses,Inhibition of Cytokine Action:,Cytokines are secreted polypeptides that co-ordinate important aspects of the immune response,including inflammation,cellular activation,proliferation,diff

7、erentiation,&chemotaxis.,Some viruses are able to inhibit the expression of certain chemokines directly.,Herpesviruses&poxviruses encode viroceptors-virus homologs of host cytokine receptors which compete with cellular receptors for cytokine binding but fail to give trans-membrane signals.,High-affi

8、nity binding molecules may also neutralize cytokines directly,&molecules known as virokines block cytokine receptors again without activating the intracellular signalling cascade.,Academic Press,2000.,Evasion of Immune Responses by Viruses,Interference with Apoptosis,Virus Resistance to Interferons:

9、,Epstein-Barr virus EBER RNAs are similar in structure&function to the adenovirus VA RNAs.,The EBNA-2 protein also blocks interferon-induced signal transduction,Vaccinia virus is known to show resistance to the antiviral effects of interferons.,One of the early genes of this virus,K3L,encodes a prot

10、ein which is homologous to eIF-2,which inhibits the action of PKR.In addition,the E3L protein also binds dsRNA&inhibits PKR activation,Poliovirus infection activates a cellular inhibitor of PKR in virus-infected cells,Reovirus capsid protein,3 is believed to sequester dsRNA&therefore prevent activat

11、ion of PKR,Academic Press,2000.,Evasion of Immune Responses by Viruses,Evasion of Humoral Immunity:,Although direct humoral immunity is less significant than cell-mediated immunity,the anti-viral action of ADCC&complement make this a worthwhile target to inhibit.,The most frequent means of subvertin

12、g the humoral response is by high frequency genetic variation of the B cell epitopes on antigens to which antibodies bind.,This is only possible for viruses which are genetically variable,e.g.influenza virus&HIV.,Herpesviruses use alternative strategies such as encoding viral Fc receptors to prevent

13、 Fc-dependent immune activation.,Academic Press,2000.,Evasion of Immune Responses by Viruses,Evasion of the Complement Cascade:,Poxviruses,herpesviruses&retrovirus families encode mimics of normal regulators of complement activation proteins,e.g.secreted proteins which block C3 convertase assembly&a

14、ccelerate its decay.,Poxviruses can also inhibit C9 polymerization,preventing membrane permeabilization.,Academic Press,2000.,Virus-Host Interactions,For all viruses,pathogenic or non-pathogenic,the first factor which influences the course of infection is the mechanism&site of entry into the body:,A

15、cademic Press,2000.,The Skin:,Mammalian skin is a highly effective barrier against viruses.,The outer layer(epidermis)consists of dead cells&therefore does not support virus replication.,Very few viruses infect directly by this route unless there is prior injury such as minor trauma or puncture of t

16、he barrier,such as insect or animal bites or subcutaneous injections.,Some viruses which do use this route are herpes simplex virus&papillomaviruses,although these viruses probably still require some form of disruption of the skin such as small abrasions or eczema.,Academic Press,2000.,Mucosal Membranes:,The mucosal membranes of the eye&genitourinary(GU)tract are much more favourable routes of access for viruses to the tissues of the body.,This is reflected by the number of viruses which can be