chapter 32 Viral Pathogenesis Samar Abu Ouda 20060282

Pathogenesis & Immunopathogenesis **The signs and symptoms of most viral diseases undoubtedly are the result of cell killing by virus-induced inhibition macromolecular synthesis e. g. poliovirus, Ebola virus

However, there are some diseases that • are not caused by the virus damaging or killing the infected cell. For example, rotavirus-induced diarrhea • is caused primarily by stimulation of the enteric nervous system.

ü There are other diseases in which cell killing by immunological attack plays an important role in pathogen ü Both T cells and antibodies play role in immunopathogensis. � (1)lymphocyte chorio meningitis (LCM) in mice (2)Cytotoxic T cells are involved in the pathogenesis of hepatitis caused by hepatitis A, B, and C viruses. (3) Immune-mediated pathogenesis

Virulence ü Strains of viruses differ greatly in their ability to cause disease For example, there are strains of poliovirus that have mutated sufficiently such that they have lost the ability to cause polio in immunocompetent individuals;

Evasion of Host Defenses vimmune evasion v. Some viruses encode the receptors for various mediators of immunity such as interleukin-I (IL-1) and tumor necrosis factor (TNF). v. Cytokine decoys ve. g. vaccina viruses , fibroma viruses

v. In addition, some viruses (e. g. , HIV, cytomegalovirus- virus) can reduce the expression of class I MHC proteins, thereby reducing the ability of cytotoxic T cells to kill the virus-infected cells, and others (e. g. , herpes simplex virus) inhibit complement. v. Several viruses (HIV, Epstein-Barr virus, and adenovirus) synthesize RNAs that block the phosphorylation of an initiation factor (el. F-2), which reduces the ability of interferon to block viral replication

v. A third important way by which viruses evade our host defenses is by having multiple antigenic types (also known as multiple serotypes). ve. g. influenza virus, rhinovirus v. Many have one serotype (poliovirus)

Persistent Viral Infections v The mechanisms that may play a role in the persistence of viruses include : v (1) integration of a DNA provirus into host cell DNA, as occurs with retroviruses; v (2) immune tolerance, because neutralizing antibodies are not formed; v (3) formation of virus-antibody complexes, which remain infectious

v (4) location within an immunologically sheltered "sanctuary, " e. g. , the brain; v (5) rapid antigenic variation; v (6) spread from cell to cell without an extracellular phase, so that virus is not exposed to antibody; v (7) immunosuppression, as in AIDS. There three of viral infections of

Ø There are three types of persistent viral infections of clinical importance: A. CHRONIC-CARRIER INFECTIONS B. LATENT INFECTIONS C. SLOW VIRUS INFECTIONS

CHRONIC-CARRIER INFECTIONS üSome patients who have been infected with certain viruses continue to produce significant amounts of the virus for long periods. ü This carrier state can follow an asymptomatic infection as well as the actual disease and can itself either be asymptomatic or result in chronic illness. ü Important clinical examples chronic hepatitis B, C

. LATENT INFECTIONS üthe patient recovers from the initial infection and virus production stops. Subsequently, the symptoms may recur, accompanied by the production of virus. üthe herpes virus

. SLOW VIRUS INFECTIONS • SLOW? ? the virus has been shown to have a normal, not prolonged, growth cycle. Two of these diseases are caused by conventional viruses: ü, subacute sclerosing panencephalitis, which follows several years after measles üprogressive multifocal leukoen- cephalopathy (PML)

Subacute sclerosing panencephalitis (SSPE) SSPE is caused by an unusual response to the • measles virus, which reactivates in the brain, often many years after the original infection. The presence of the virus within the brain cells prevents them working properly and passing. messages to each other.