VIRAL IMMUNOLOGY Prepared by : Mustafa Flaifel Presented to : Prof. Joma’a Shakhanbeh

Objectives : * INRODUCTION : What is the virus?, Virus Structure, and Viral genome. * Cellular Responses to Viral Pathogens * Immunopathogenesis of Viral Infection * Innate Immunity Against Viral Pathogens * Mechanisms of Host Invasion, Evasion, and Resistance (including HIV)

What is the virus? A virus is a small infectious agent that replicates only inside the living cells of other organisms. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

Virus Structure All viruses contain the following two components: 1) a nucleic acid genome 2) a protein capsid that covers the genome. Together this is called the nucleocapsid. 3) In addition, many animal viruses contain a lipid envelope.

Viral structure of some viruses

Several types of viral genomes

Cellular Responses to Viral Pathogens Cellular Responses to Viral Pathogens pass through two phases : 1- Activation phase 2- Effector phase

Immunopathogenesis of Viral Infection Immunopathogenesis : It can be defined as the damage caused to an organism by its own immune response to an viral infection.

Pathogenesis The ability of viruses to cause disease can be viewed on two distinct levels : (1)The changes that occur within individual cells. (2) The process that takes place in the infected patient.

THE INFECTED CELL 1.Death. 2. Fusion of cells to form multinucleated cells. 3. Malignant transformation. 4. No apparent morphologic or functional change.

A- Death of the cell is probably due to inhibition of macromolecular synthesis. Inhibition of host cell protein synthesis frequently occurs first and is probably the most important effect. Inhibition of DNA and RNA synthesis may be a secondary effect. it is important to note that synthesis of cellular proteins is inhibited but viral protein synthesis still occurs. For example : - Poliovirus indicates an initiation factor (IF) required for cellular mRNA to be translated into cellular proteins. - poliovirus mRNA has a special ribosome-initiating site that allows it to pass the IF so that viral proteins can be synthesized.

- Infected cells frequently contain inclusion bodies, which are discrete areas containing viral protein or viral particles. -They have a characteristic interanuclear or intracytoplasmic location and appearance depending on the virus. - One of the best examples of inclusion bodies that can assist in clinical diagnosis is that of Negri bodies. Which are eosinophilic cytoplasmic inclusion found in rabies virus-infected brain neurons. -Another important example is the owls eye inclusion seen in the nucleus of cytomegalovirus-infected cells. B- Fusion of virus-infected cells produces multinucleated cells, which characteristically form after infection with herpesviruses and paramyxoviruses.

Negri bodies cellular inclusion of rabies infection owls eye inclusion seen in the nucleus of cytomegalovirus-infected cells.

Tzanck Smear show multinucleated giant cell

-The clinical diagnosis of herpesvirus skin infections is aided by the finding of multinucleated gaint cells with eosinophilic intranuclear inclusions in skin scrapings. -Ahallmark of viral infection of the cell is the cytopathic effect (CPE). -This change in the appearance of the infected cell usually culminates in either lysis or gaint cell formation. - Detection of virus in a clinical specimen frequently is based on the appearance of CPE in cell culture.

C - infection with certain viruses causes malignant transformation which is characterized by unrestrained growth, prolonged survival, and morphologic changes. D – infection of the cell accompanied by virus production can occur without morphologic or gross functional changes.

Innate Immunity Against Viral Pathogens Defense against viruses is provided by type I interferons and natural killer cells. Type I interferons inhibit viral replication, and induce an antiviral state, in which cells become resistant to infection. Type I IFNs, which include several forms of IFN-α and one of IFN-β, are secreted by many cell types infected by viruses.

A major source of these cytokines is a type of dendritic cell called the plasmacytoid dendritic cell, which secretes type I IFNs when activated by recognition of viral nucleic acids by TLRs and other receptors. When type I IFNs secreted from dendritic cells or other infected cells bind to the IFN receptor on the infected or adjacent uninfected cells, signaling pathways are activated that inhibit viral replication and destroy viral genomes

This action is the basis for the use of IFN-α to treat some forms of chronic viral hepatitis. Virus-infected cells may be destroyed by NK cells, as described earlier. Type I IFNs enhance the ability of NK cells to kill infected cells. In addition, part of the innate response to viral infections includes increased apoptosis of infected cells, which also helps to eliminate the reservoir of infection. S

Antiviral actions of type I interferons. Type I interferons (IFN-α, IFN-β) are produced by plasmacytoid dendritic cells and virus- infected cells in response to intracellular TLR signaling and other sensors of viral nucleic acids. Type I interferons bind to receptors on the infected and uninfected cells and activate signaling pathways that induce expression of enzymes that interfere with viral replication at different steps, including inhibition of viral protein translation, increasing viral RNA degradation, and inhibition of viral gene expression and virion assembly. Type I IFNs also increase the infected cell’s susceptibility to CTL-mediated killing (not shown).

Mechanisms of Host Invasion, Evasion, and Resistance (including HIV) Mechanisms of Host Invasion:

Mechanisms of Host Evasion 1- Antigenic variation :

2- Infection and death or functional impairment of immune cells. 3- Inhibition of complement activation : -Recruitment of factor H -Incorporation of CD59 in viral envelope. 4- Inhibition of innate immunity : -Inhibition of access to RIG -1 -RNA sensor -Inhibition of PKR (signaling by INF receptor )