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.

Modes of Transmission of Viruses1- 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)

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).

Expressions

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

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A. Acute infection ClearanceVi

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D. slow chronic infectionB. Acute infection chronic infection

C. Acute infection Latency Reactivation

Smallpox( آبانسانی (له

Varicella- Zoster

سرخک مزمن

Hepatitis- B

Types of infection

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

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

2- Viral transfer in the body

• Blood stream

• Mononuclear phagocyte

• Lymphatic system

• NeuronsBlood stream and lymphatic system are the predominant means of viral

transfer in the body

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,,,

Types and Properties of Interferon

Interferon

Property Alpha Beta Gamma

Principal source Leukocytes, Epithelium Fibroblasts Lymphocytes

pH stability Stable Stable Labile

InducersViruses (RNA>DNA)dsRNA

Viruses(RNA>DNA)dsRNA

Antigens, Mitogens

Interferon

- glycoproteins, inhibit mRNA translation to proteins

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

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

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)

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.

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)

Herpes virus lesion on the chorioallantoic membrane

Laboratory animals

• Mice and guinea pig are models for most viruses

• Injection (cutaneous, sub- cutaneus and peritoneal )

Measuring the Sizes of VirusesDirect 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.

Hepatitis B virus

EM picture of rabies virus

Virus Isolation

Cell Cultures are most widely used for virus isolation, there are 3 types of cell cultures:

1. Primary cells - e.g., Monkey Kidney2. Semi-continuous cells - Human embryonic kidney and skin fibroblasts3. 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.

Treatment and Prevention of Virus Infections

• Antivirals

• Vaccines and immunisation

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)

(HIV, HBV, HIV)

(HSV, CMV)

(HIV)

Problems with Antivirals

• Identification of virus-specific target.

• Generation of resistant variants.

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 virus1. Isolation of specific protein2. Recombinant administration