Viral disease

Physical Defenses Against Viral Infection

skin, mucus, ciliated epithelium, gastric acid and bile

bile

detergent - dissolves fats/lipids in enveloped viruses

Antigen-Non-Specific Antiviral Response

interferon, cytokines TNF and IL-1, NK cells, macrophages and fever

fever

Viruses have evolved to replicate at 37 degrees C so fever inhibits replication

Antigen-Specific Immune Responses

Include the T cell response and antibodies

Immunopathogenesis

immune-mediated mechanisms that contribute to viral infection-related problems, such as flu-like symptoms, delayed hypersensitivity and inflammation

Interferons

Proteins that initiate an antiviral state in cells, inhibit viral protein synthesis, and have immunomodulatory functions

α-interferons

acid stable, non-glycosylated proteins produced by leukocytes in response to dsRNA viruses

β-interferons

acid stable glycoproteins produced by fibroblasts in response to viral infection and bacterial components TNF and IL-1

γ interferon

acid-labile glycoprotein produced by T and NK cells in response to antigens, mitogens and IL-2

What causes interferon induction?

dsRNA, viral inhibition of cellular protein synthesis, or enveloped viruses interacting with a rare blood leukocyte

How do interferons help induce the antiviral state after release from infected cell?

bind receptor on other cell → protein kinase, 2’-5’ oligoadenylate synthase and ribonuclease L synthesised

basic steps in viral disease

acquisition, infection initiation, incubation period, target tissue infection

What is access of virus to target tissue dependent on?

entrance portal, ability to cross mucous epithelial cells, virus stability, ability to establish viraemia, tissue tropism and host permissiveness

viral stability

ability of a virus to withstand body temperature, host defences and acid and bile

Tissue Tropism

specificity of viral attachment proteins and the expression of receptors in specific tissues

abortive viral infection

no virus produced, no effect on host cell

transformation viral infection

no virus produced, host cell becomes tumour cell

cytolytic viral infections

classical viral infections where viral production occurs eventually leading to cell death

chronic persistent viral infection

viral production and host cell senescence, which is where the virus is slowly released from the host cell without cell death

persistent latent viral infection

doesn’t lead to viral production, no effect on host cell. Virus emerges later in a cytolytic infection

Cytopathological Activity of Viruses

cell lysis, changes in macromolecular synthesis → accumulation of cytotoxic viral proteins, histological changes eg vacuolisation, and apoptosis

What is viral cytopathological activity dependent on?

efficiency of viral replication in the cell

polioviruses and poxviruses

inhibit protein synthesis

herpesviruses

inhibit and degrade DNA

enveloped viruses

alter membrane structure eg by inserting glycoproteins, disrupting cytoskeleton, changing permeability or forming syncytia

inclusion bodies

overexpressed tangle of viral proteins within which virus particles sometimes become trapped

intracytoplasmic negri bodies

produced by rabies

intranuclear owl eyes

produced by human herpesvirus 5

intranuclear Cowdy type A bodies

produced by measles

intranuclear basophilic bodies

produced by adenoviruses

intranuclear acidophilic bodies

produced by poxviruses

perinuclear cytoplasmic acidophilic bodies

produced by Togaviruses

asymptomatic viral cases

Infection controlled before virus reaches target tissue. Target tissue expendable and damaged tissue rapidly repaired so extent of damage below functional threshold. Still can spread infection

Viral Transmission Mechanisms (from lowest viral fragility to highest)

aerosols, food and water, fomites eg tissue/clothes, sexual/direct contact with bodily fluids, birth, blood transfusion/injection/organ transplant, zoonoses and genetic transmission

Why are naked viruses more likely to be transmitted by aerosol?

Much more resistant to environment than enveloped viruses