Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Viruses and Immunodeficiency
Document related concepts
Transcript
Virus Pathogenesis • How virus infection may injure the body • How HIV infection causes AIDS • How some viruses cause cancer • Emergent viruses Principles of Molecular Virology © Elsevier, 2011. Mechanisms of Cellular Injury • Altered shape • Detachment from the substrate • Lysis • Membrane fusion • Membrane permeability • Inclusion bodies • Apoptosis Principles of Molecular Virology © Elsevier, 2011. Viruses and Immunodeficiency HIV and AIDS Principles of Molecular Virology © Elsevier, 2011. HIV and AIDS • HIV infects CD4+ cells • CD4 + cells are constantly being eliminated by HIV infection while the body is constantly replacing them • Over time, CD4 counts drop, leaving the body susceptible to the infections that define AIDS • Antigenic variation is important in the biology of HIV Principles of Molecular Virology © Elsevier, 2011. Virus-Related Diseases - SSPE Measles - subacute sclerosing panencephalitis (SSPE) (about 1 in 300,000 cases): – Virus replication continues at a low level, but defects in the envelope protein genes prevent the production of extracellular infectious virus particles – Lack of envelope protein production causes failure of the immune system to recognize and eliminate infected cells Principles of Molecular Virology © Elsevier, 2011. Virus-Related Diseases - Dengue Principles of Molecular Virology © Elsevier, 2011. Bacteriophages and Human Disease • Stx1 and Stx2 toxin genes are encoded by lysogenic prophages in Escherichia coli Other bacterial virulence determinants are also encoded by lysogenic phages: • Diphtheria toxin • Streptococcus erythrogenic toxins • Staphylococcus enterotoxins Principles of Molecular Virology © Elsevier, 2011. Cell Transformation by Viruses Transformed cells have an altered phenotype: • Loss of anchorage dependence • Loss of contact inhibition • Colony formation in semi-solid media • Decreased requirements for growth factors Principles of Molecular Virology © Elsevier, 2011. Cell Transformation by Viruses Transformation is mediated by proteins encoded by oncogenes: • Oncogenes and proto-oncogenes • Tumour suppressor genes • DNA repair genes Principles of Molecular Virology © Elsevier, 2011. Oncogenes Principles of Molecular Virology © Elsevier, 2011. Oncogenes Principles of Molecular Virology © Elsevier, 2011. Cell Transformation by Retroviruses Not all retroviruses are capable of transforming cells (e.g. HIV) • Transduction • Cis-activation • Trans-activation Principles of Molecular Virology © Elsevier, 2011. Cell Transformation by DNA Viruses • Several families of DNA viruses are capable of transforming cells • Interact with cellular proteins which have a negative regulatory role in cell proliferation - p53 and pRb Principles of Molecular Virology © Elsevier, 2011. SV40 T-antigen Binds to p53, allows DNA replication Principles of Molecular Virology © Elsevier, 2011. DNA Transforming Viruses • Adenoviruses • Human papillomavirus (HPV) Principles of Molecular Virology © Elsevier, 2011. Viruses and Cancer • Epstein Barr Virus (EBV) • Hepatitis B Virus (HBV) • Hepatitis C Virus (HCV) • Human Herpesvirus 8 (HHV-8) • Human Papillomaviruses (HPV) • Human T-Cell Leukaemia Virus (HTLV) Principles of Molecular Virology © Elsevier, 2011. New and Emergent Viruses • Poliovirus - changed with time? • Measles virus • Smallpox virus Principles of Molecular Virology © Elsevier, 2011. Arboviruses • • • • Yellow fever virus Hantaviruses West Nile virus Chikungunya virus Principles of Molecular Virology © Elsevier, 2011. Zoonoses • Many emergent virus diseases are zoonoses (transmitted from animals to humans) • Ebola virus (1976) • Severe acute respiratory syndrome (SARS) (2003) Principles of Molecular Virology © Elsevier, 2011. Bioterrorism? • Smallpox • Haemorrhagic fevers - filoviruses and arenaviruses Principles of Molecular Virology © Elsevier, 2011. Summary • Virus pathogenesis is complex, variable, relatively rare • Pathogenesis is determined by the balance between host and virus factors • The immune system also plays a part in causing symptoms and damage • Some viruses can transform cells so that they continue to grow indefinitely • Approximate 20% of human cancers are thought to be due to viruses Principles of Molecular Virology © Elsevier, 2011. Further Reading Best, S.M. (2008) Viral Subversion of Apoptotic Enzymes: Escape from Death Row. Annual Review of Microbiology 62: 171-192 Casadevall, A. and Pirofski, L.A. (2004) The weapon potential of a microbe. Trends in Microbiology, 12: 259–263 Coiras M., López-Huertas M.R., Pérez-Olmeda, M. and Alcamí, J. (2009) Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nature Reviews Microbiol. 7(11): 798-812 DeCaprio, J.A. (2009) How the Rb tumor suppressor structure and function was revealed by the study of Adenovirus and SV40. Virology 384(2): 274284 Donlan, R.M. (2009) Preventing biofilms of clinically relevant organisms using bacteriophage. Trends in Microbiol. 17(2): 66-72 Douek, D.C. et al. (2003) T cell dynamics in HIV-1 infection. Annual Review of Immunology, 21: 265–304 Forsman, A. and Weiss R.A. (2008) Why is HIV a pathogen? Trends Microbiol. 16(12): 555-560 Hay, S. and Kannourakis, G. (2002) A time to kill: viral manipulation of the cell death program. J Gen Virol. 83: 1547-1564 Jansen, K.U. and Shaw, A.R. (2004) Human papillomavirus vaccines and prevention of cervical cancer. Annual Review of Medicine, 55: 319–331 Kyle, J.L. and Harris E. (2008) Global spread and persistence of dengue. Ann Rev Microbiol. 62: 71-92 LaBeaud, A.D., Kazura, J.W. and King, CH. (2010) Advances in Rift Valley fever research: insights for disease prevention. Curr Opin Infect Dis. 23(5): 403-408 Racaniello, V.R. (2006) One hundred years of poliovirus pathogenesis. Virology. 344(1): 9-16 Randolph, S.E. and Rogers, DJ. (2010) The arrival, establishment and spread of exotic diseases: patterns and predictions. Nat Rev Microbiol. 8(5): 361-371 Sierra, S., Kupfer, B. and Kaiser, R. (2005) Basics of the virology of HIV-1 and its replication. J Clin Virol. 34(4): 233-244 Stephen, A., Mims, C.A. and Nash, A. (2000) Mims’ Pathogenesis of Infectious Disease, 5th ed. Academic Press, London. ISBN 0124982654 Thorley-Lawson, D.A. and Allday, M.J. (2008) The curious case of the tumour virus: 50 years of Burkitt's lymphoma. Nature Rev Microbiol. 6(12): 913-924 Weaver, S.C and Reisen, W.K. (2010) Present and future arboviral threats. Antiviral Res. 85(2): 328-345. Weiss, R.A. (2002) Virulence and pathogenesis. Trends in Microbiology, 10: 314–317 Whitehead, S.S., Blaney, J.E., Durbin, A.P. and Murphy, B.R. (2007) Prospects for a dengue virus vaccine. Nature Rev Microbiol. 5(7): 518-528 Principles of Molecular Virology © Elsevier, 2011.
