1. Bioterrorism Agents Bioterrorism agents are microorganisms (or toxins) that could be used to produce death and disease in humans, animals, or plants for terrorist purposes Viral agents in the highest risk category are smallpox and the viral hemorrhagic fevers highest risk bacteria include the agents of anthrax, botulism, plague, and tularemia.

2. Modes of Transmission of Viruses 1- Direct transmission from person to person by contact : By droplet or aerosol(Inf, VZV, Rubella, measles, smallpox) by sexual contact (HPV, HBV, HSV-2, HIV) by hand–mouth, hand–eye, or mouth–mouth contact ( HSV, rhinovirus, EBV) by exchange of contaminated blood ( HBV, HIV)

3. Modes of Transmission of Viruses 2- Indirect transmission by the fecal–oral route ( enteroviruses, rotaviruses, infectious hepatitis A) or by fomites ( Norwalk virus, rhinovirus) 3- Transmission from animal to animal, with humans an accidental host. Spread may be by bite (rabies) or by droplet or aerosol infection from rodent (arenaviruses, hantaviruses) 4- Transmission by means of an arthropod vector (Arboviruses).

4. Expressions - Vertical transmission (congenital infections) - Horisontal transmission - Latency period or phase - Eclipse phase

5. Virus measure time Virus measure time A. Acute infection Clearance Virus measure time Virus measure time D. slow chronic infectionB. Acute infection chronic infection C. Acute infection Latency Reactivation Smallpox( آبله انسانی ) Varicella- Zoster سرخک مزمن Hepatitis- B Types of infection

6. Viral Pathogenesis Viral pathogenesis is the process by which a viral infection leads to disease Factors in Viral Pathogenesis Viral entry pathways Viral transfer in the body Host Immune Response Virus Clearance or Persistence

7. 1- Viral Entry Skin - Most viruses which infect via the skin require a breach in the physical integrity of this effective barrier, e.g. cuts or abrasions. Rabis, Arboviruses Conjunctiva and other mucous membranes : Measles, Adeno, Herpes Respiratory tract : Influenza Gastrointestinal tract : Entroviruses Genital tract: HIV, HBV, HSV-2 Placental transfer: Rubella, CMV Blood transfer: HIV, HBV

8. 2- Viral transfer in the body Blood stream Mononuclear phagocyte Lymphatic system Neurons Blood stream and lymphatic system are the predominant means of viral transfer in the body

9. 2- Host immune response Immune system - protects us against foreign material proteins, viruses, bacterial infections Immune system has two major divisions. - Non-Specific Response - block entry of foreign agents into the body - block the spread of foreign agents if they get into the body Interferon's, fever, hypoxia and,,,

10. Types and Properties of Interferon Interferon Property AlphaBetaGamma Principal source Leukocytes, Epithelium FibroblastsLymphocytes pH stabilityStable Labile Inducers Viruses (RNA>DNA) dsRNA Viruses(RNA>DNA ) dsRNA Antigens, Mitogens Interferon - glycoproteins, inhibit mRNA translation to proteins

11. Humoral Immunity Involves antibodies (secreted from B cells) Cell-Mediated Immunity Involves the activities of specific white blood cells (T cells). - Specific Responses - antibody-mediated immunity - humoral response - cell-mediated immunity – cellular response

12. 4- Virus Clearance or Persistence A persistent infection occurs in an infected cell that is not killed by virus. These viruses released from the through exocytosis or through budding Viral infection may cause chronic disease( persistent infection ). The ability and speed with which a persons immune system controls and resolves a viral infection

13. Detection of Virus-Infected Cells Cytopathic effects, ie, morphologic changes in the cells. - Cell lysis or necrosis, inclusion formation, giant cell formation, and cytoplasmic vacuolization (Light microscope). Appearance of a virus-encoded protein, - Hemagglutinin of influenza virus Detection of virus-specific nucleic acid. - Polymerase chain reaction (PCR) Viral growth in an embryonated chick egg may result in: - Death of the embryo (eg, encephalitis viruses), - Production of pocks or plaques on the chorioallantoic membrane (eg, herpes, smallpox, vaccinia)

14. Inclusion Body Formation  During viral multiplication within cells, virus-specific structures called inclusion bodies may be produced. They may be situated in the nucleus (herpesvirus), in the cytoplasm (poxvirus), or in both (measles virus). The intracytoplasmic inclusion in nerve cells—the Negri body—is pathognomonic for rabies.

15. Cytopathic Effect (1) Cytopathic effect of enterovirus 71 and HSV in cell culture: note the ballooning of cells. (Virology Laboratory, Yale-New Haven Hospital, Linda Stannard, University of Cape Town)

16. Herpes virus lesion on the chorioallantoic membrane

17. Laboratory animals Mice and guinea pig are models for most viruses Injection ( cutaneous, sub- cutaneus and peritoneal )

20. Measuring the Sizes of Viruses Direct observation in the electron microscope is the most widely used method for estimating particle size. Another method that can be used is sedimentation in the ultracentrifuge.

21. Hepatitis B virus

22. EM picture of rabies virus

23. Virus Isolation Cell Cultures are most widely used for virus isolation, there are 3 types of cell cultures: 1. Primary cells - e.g., Monkey Kidney 2. Semi-continuous cells - Human embryonic kidney and skin fibroblasts 3. Continuous cells - HeLa, Vero, Hep2  Primary cell culture, best cell culture systems available since they support the widest range of viruses. However, they are very expensive  Continuous cells are the most easy to handle but the range of viruses supported is often limited.

24. Treatment and Prevention of Virus Infections Antivirals Vaccines and immunisation

25. Antiviral Targets Attachment/Entry/fusion ( enfuvirtide, HIV ) Uncoating ( Amantadin, Inf ) Nucleic acid replication ( Acyclovir, HSV ) Integration in host genome ( integrase inhibitor, HIV ) Virus maturation/budding ( oseltamivir, INf )

26. (HIV, HBV, HIV) (HSV, CMV) (HIV)

27. Problems with Antivirals Identification of virus-specific target. Generation of resistant variants.

29. Types of Viral Vaccines 1.Inactivated: Virus particles are grown then killed by either heat or formaldehyde 2.Attenuated: Live, weakened form of the virus particles 3.Subunit: Only given antigen of virus 1.Isolation of specific protein 2.Recombinant administration