MICR 201 Microbiology for Health Related Sciences

1. MICR 201 Microbiology for Health Related Sciences Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010 Chapter 13: Viral pathogenesis

2. Why is this chapter important? • Because viral infections are so prevalent in humans, health care professionals must understand the pathogenic mechanisms used by these pathogens.

3. Map for chapter 13

4. Patterns of viral infections: course of infection • Viral infections can be: • Acute (rapid and self limiting) • Sometimes latent infection can develop • Persistent (long term) • Chronic • Latent • Slow • Transforming (leading to cancer)

5. Viruses and cancer • Cancer is essentially associated with mutations that cause uncontrolled growth. • Normal cell undergo contact inhibition. • Some viruses can cause cancer in animals (transforming viruses) by altering control mechanisms for cell division and cell death or inactivating genes responsible for suppressing tumor formation • Oncogenic viruses • An estimated 20% of human cancers involve viruses. • HBV, HCV: liver carcinoma • EBV: lymphoma • HPV: cervix carcinoma

6. Patterns of viral infections: damage to host cell • Cytopathic viruses produce virions and kill host cells rapidly (cytopathology). • Noncytopathic viruses produce virions but do not cause apparent cytopathology. • Some viruses do not produce virions or cause cytopathology but still cause infection.

7. Viral cytopathic effect • Virus induced changes of eukaryotic cell morphology • Cell rounding • Cell aggregation • Inclusion bodies • Negri bodies in rabies • Cell fusion (syncytium) Normal Cell rounding

8. Patterns of acute viral infection • Incubation period: • The virus is replicating. • The host is beginning to respond. • Acute infection: • Characterized by rapid production of virions and action of host defense • Depending on virus not every infected person develops symptoms (positive antibody titers without recollection of an acute infection) • Decline and convalescence • Elimination of virus infected cells • Development of long lasting immune response

9. Patterns of viral infections • Incubation periods for viral diseases vary for different viruses. • Some are as short as days: • Influenza • Common cold • Some are as long as years: • AIDS Days Weeks Months Years

10. Course of a typical acute viral infection Long lasting protection against the same virus type (days)

11. Re-infection due to antigenic variation • There are two forms of antigenic variation (well described for influenza virus): • Antigenic drift: Involves small changes in virion structure • Results from point mutations • Minor changes • Cross protective immunity still exists • Antigenic shift: Involves major changes in virion structure • Is due to the acquisition of new genes • This is through co-infection and gene re-assortment • No pre-existing immunity

12. Antigenic drift versus Antigenic shift http://upload.wikimedia.org/wikipedia/commons/c/ca/Antigenic_drift_vs_shift.png

13. Antigenic drift versus antigenic shift • Movie clips\13.01_Antigenic_Drift.mov • Movie clips\13.02_Antigenic_Shift.mov

14. Viruses that lead to the death of the host cell they infect shortly after infection are called _____ viruses. • non-cytopathic • persistent • cytopathic • latent • permissive

15. When changes in virion structure occur as a result of major genetic changes, this is called _____. • antigenic drift • mutational shift • conformational mutagenesis • antigenic shift • None of the above.

16. Problems of acute viral infections • Acute viral infections are severe public health problems. • They are usually associated with epidemics. • They are more often seen in crowded environments • Schools, nursing homes, military • Often virus is spread before symptoms arise. • Sometimes virus can disseminate to various tissues, go into latency and later on re-appear • Example: varicella-zoster (chicken pox).

17. Acute viral infection leads to latency and re-activation: varizella-zoster virus Chicken pox Shingles

18. Persistent viral infections • Occur when host defenses are either modulated or completely bypassed. • Virions are produced for months or even years. • There are variations of persistent infections: • Chronic infection – the infection is eventually cleared • Latent infection – the infection lasts for life • Slow infections – these infections are usually associated with fatal brain infections • Transforming – virus infection triggers cancer development

19. Persistent viral infections in humans

20. Persistent viral infections HBV – liver cirrhosis EBV Burkitt lymphoma HSV – cold sores Measles encephalitis

21. Persistent viral infection: evasion of cytotoxic T lymphocytes (CTLs) • Adaptive host defense mechanisms against viral infection include cytotoxic T cells. • CTLs detect specific virus infected cells and instruct the cell to commit suicide. • Some viruses mutate specific proteins making them unrecognizable (CTL escape mutants). • Some viruses trigger instead suicide of the CTL. • Other viruses infect in areas that lack local adaptive defense, e.g. top skin layers, brain.

22. Persistent viral infections: latent Infections • Three general characteristics: • No large-scale production of virions • Reduced or absent immune response • Persistence of an intact viral genome so infections can reoccur • Latent viruses can be reactivated years after entry into host. • Examples are herpes simplex virus and varizella zoster virus • Use neurons as vehicles • Remain as extrachromosomal elements in the host nucleus

23. Viral dissemination • Viruses can spread easily within the body • Blood • “Hematogenous dissemination” with viremia • Lymph • Hidden within mobile immune cells (lymphocytes, monocytes) • Neural network (axons, dendrites) • Peripheral neurons central nervous system • Olfactory nerve central nervous system • Blood central nervous system

24. Viral dissemination via blood • Local replication at portal of entry • Primary viremia • Organ replication • Secondary viremia • Organ replication Viral rashes are result of spread into skin after viremia.

26. Chapter 13 key concepts • Viral infections can be acute or persistent. • Persistent infections last longer and can be chronic, latent, slow, transforming • Cytopathic viruses kill host cells when they release new virions, whereas non-cytopathic viruses do not cause cell death even though they are releasing new virions. • Latent viral infections do not produce large numbers of virions, but these infections can be reactivated later and release virions.

27. Chapter 13 key concepts Viruses can be disseminated (move to other parts of the infected host’s body) through the respiratory, digestive, and urogenital tracts as well as the nervous system. This is reflected in the skin rashes associated with many viral infections. Some oncogenic viruses have been implicated in the development of malignancies.

28. Midterm – Wednesday, March 1 • 11:40am – 1:20pm • Chapters 1 thru 13: Lecture, Reading, Chapter End Self Study Questions • Fifty Multiple Choice Questions = 100 points • Please bring: • Scantron (form No. 882-E for the Quiz – available at no cost at the Student Bookstore) • No. 2 pencil only