Virology lecture 3 Flashcards
8 commonly used viral portals of entry and exit
1 - oropharynx - HSV, HCMV, EBV
2 - respiratory tract - influenza, measles, mumps, rubella, rhinovirus,VZV, some adenoviruses
3 - alimentary canal - poliovirus, hep A (HAV), rotavirus, some adenoviruses
4 - conjunctiva - HSV
5 - skin - HPV, HSV, rabies
6 - genital tract - HIV, HSV, HPV
7 - blood, iatrogenic - HBV, HIV
8 - blood, biting insects - yellow fever virus, dengue virus, bluetounge virus
physical barriers to infection
skin, cilia, mucous secretions, proteases, low pH. viruses are well adapted to their route of entry, eg poliovirus is v. resistant to low pH of the stomach and proteases.
7 componants of innate immunity vs viruses
1 - phagocytes - phagocytose free particles or infected cells and debris. some viruses can grow in macrophages
2 - complement
3 - interferon (IFN) - promote adaptive immunity and put cells into antiviral state
4 - apoptosis of infected cells
5 - cytokines - promote inflammation and Th1 response
6 - chemokines - recruit leukocytes
7 - NK cells - lyse infected cells in antigen dependent manner
8 - fever - restrict replication of some.
how is a viral infection sensed, cellular cascade
PRRs bind PAMPs, activate TFs such as NF-kB or interferon response factors (IRFs). these promote transcription inc - IFNbeta, chemokines, inflammatory cytokines (IL-1beta, TNF)
interferon classes and general functions
species specific soluble glycoproteins.
1 - type 1 - IFNalpha and beta - released by infected cells, binds type 1 IFNR on adjacent cells - induce antiviral state and up-regulate class 1 MHC
2 - type 2 - IFNgamma - released by activated T cells and macrophages, binds IFNgammaR, promotes inflammation and Th1 response
3 - type 3 - IFNlambda - binds the type 3 R, imp in epithelial cells.
the vast majority of mammalian viruses have at least one mech of blocking IFN action.
IFNalpha/beta binding to its R induces what?
induces the JAK-STAT signalling pathway - activates ‘interferon stimulated gene factor 3 (ISGF-3). - binds interferon stimulated response element (ISRE) present in many interferon stimulated genes (ISGs).
proteins generated inc - PKR, OAS and the Mx protein.
PKR and OAS are activated by viral dsDNA and inhibit all cellular protein synthesis - cell death.
viral mechanisms of interfering with IFNs?
1 - blocking PRR signal cascades
2 - releasing soluble IFN binding proteins
3 - inhibiting JAK-STAT signalling to prevent ISG stimulation
4 - targeting the ISG proteins directly
poxviruses exhibit ALL of these
how can viruses block host cell apoptosis?
1 - block caspase action or target the Bcl-2 family of proapoptotic proteins
how do viruses block chemokines and cytokines
1 - myriad of ways. can stimulate production and secretion of proteins that bind them to neutralise. poxviruses and herpesviruses do this.
EBV expresses a viral cytokine (vIL-10) that drives the immune system to a Th2 rather than Th1 response.
contrast action of NK cells and Cytotoxic T cells briefly
NKs kill virally infected cells in an antigen independent manner. the missing self model. if class 1 MHC is absent the NK cell is disinhibited from killing the cell. some viruses have devised mechs to block the NKs. Cytotoxic T cells instead kill in an antigen dependent manner. NKs are hence v imp early in infection killing off many virally infected cells before they get the chance to start spreading.
Function of antibodies in viral infections?
bind to and neutralise viral particles to prevent infection or diminish spread. can be bound to complement too. mucosal IgA important is preventing viral infection of the respiratory system.
how do viruses block the action of cytotoxic T cells? 3 primary mechs. other NON-CD8 general mechs?
1 - block transport of peptides into the ER (HSV and adenoviruses)
2 - cause the degredation of MHC class 1 by inducing their transport back into the cytosol for proteolytic deg. (HCMV)
3 - prevent transport of MHC class 1 to the cell surface.
1 - latency - hide. (herpesviruses, retroviruses)
2 - express viral FcR to remove antibodies from circulation (herpes)
3 - antigenic variation - HIV, influenza and Hep C - all RNA so low fidelity replication.
possible outcomes of a viral infection of a cell
1 - cell death (common) - cell type infected gives rise to the specific disease
2 - cell transformation - cancer
3 - persistent infection - continues to replicate
4 - latent infection - virus remains dormant for long periods.
5 viral diseases caused by cell death outcome
1 - poliovirus - motor neurones (anterior horn in CNS) - paralysis. but only if it escapes the gut epithelium.
2 - Rotavirus - gut epithelial cells - diarrhoea
3 - HIV - CD4+ T helper cells - immunodeficiency
4 - Hepatitis B virus - Hepatocytes - acute hepatitis
5 - Rabies Virus - Perkinji cells in the cerebellum - hydrophobia and aggressive behaviour
4 viral diseases associated with latent or persistent infections of hbv, measles, hsv and vzv
1 - Hepatitis B virus - hepatocytes - chronic hepatitis predisposing for liver cancer
2 - measles virus - neurones - subacute schlerosing panencephalitis (SSPE) but this is rare (and fatal) occuring in around 1 in 300000 infections
3 - HSV-1,HSV-2 - neurones - cold sores and genital herpes
4 - Varicella-zoster virus - neurones - chickenpox and shingles