Viral disease

We have many physical defences against viral infection, including the skin, mucus, ciliated epithelium, gastric acid and bile. Bile is a detergent so dissolves fats/lipids in enveloped viruses. Antigen-non-specific antiviral response involves interferon and cytokines TNF and IL-1, natural killer cells and macrophages, and 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.

Many problems with viral infection are due to immunopathogenesis. Immune mediators of the immunopathogenesis flu-like symptoms in respiratory viruses and arboviruses = interferon and lymphokines. Immune mediators in delayed type hypersensitivity and inflammation = T cells, macrophages and polymorphonuclear leukocytes in enveloped viruses. Immune mediators of immune complex disease = antibody and complement in Hep B and Rubella. Immune mediators of haemorrhagic disease = T cell, antibody and complement in Dengue and measles. Immune mediators of post infection cytolysis = T cells in enveloped viruses. Immunosuppression occurs in HIV, measles and rubella.

Interferons initiate an antiviral state in cells, blocking viral protein synthesis and inhibiting cell growth. They also have immunomodulatory and other functions. Alpha interferons are acid-stable, non-glycosylated proteins produced by leukocytes in response to dsRNA viral infection. Beta interferons are acid stable glycoproteins produced by fibroblasts in response to viral infection and bacterial components TNF and IL-1. Gamma interferon is an acid-labile glycoprotein produced by T and NK cells in response to antigens, mitogens and IL-2.

Interferon induction occurs due to presence of dsRNA, viral inhibition of cellular protein synthesis, or enveloped viruses interacting with a rare blood leukocyte. Interferons are released from initial infected cell and bind specific receptor on another cell to induce the antiviral state by synthesising protein kinase, 2’-5’ oligoadenylate synthase, ribonuclease L. This stops protein synthesis blocking viral replication.

The basic steps in viral disease are acquisition, initiation of infection, the incubation period and finally infection of target tissue.

Access of the virus to the target tissue depends on its entrance portal, ability to cross mucous epithelial cells, stability of the virus in the body, ability to establish viraemia, tissue tropism and cellular permissiveness for virus replication.

Stability of virus is the ability of a virus to withstand body temperature, host defences and acid and bile.

Tissue tropism = specificity of viral attachment proteins and tissue specific expression of receptors.

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

Chronic persistent viral infections lead to viral production and host cell senescence, which is where the virus is slowly released from the host cell without cell death. Persistent latent viral infections do not lead to viral production and have no effect on the host cell. The virus is present but not causing harm to the cell, the virus emerges later in a cytolytic infection.

Cytopathological activity of a virus is dependent on the efficiency of viral replication in the cell. Viral cytopathological activity may be cell lysis or changes in cell macromolecular synthesis leading to accumulation of cytotoxic viral proteins, non-specific histological changes eg vacuolisation, and apoptosis.

Polioviruses and poxviruses are examples of viruses which inhibit protein synthesis. Herpesviruses inhibit and degrade DNA. Enveloped viruses alter the membrane structure, and they may do this by inserting glycoproteins, disrupting the cytoskeleton, changing the permeability or forming syncytia.

Some viruses produce inclusion bodies. These may be intracytoplasmic negri bodies (rabies), intranuclear owls eyes (Human herpesvirus 5), intranuclear Cowdy type A (measles), intranuclear basophilic (adenoviruses), intranuclear acidophilic (poxviruses) or perinuclear cytoplasmic acidophilic (Togaviruses). Inclusion bodies are an overexpressed ‘tangle’ of virus proteins within which viral particles sometimes become trapped.

Viruses range in incubation period from 1-2 days eg influenza to 1 to 10 years eg HIV.

Sometimes people are infected with a virus and seemingly unaffected. The infected tissue is undamaged and infection is controlled before the virus reaches the target tissue. Target tissue is expendable and damaged tissue is rapidly repaired meaning the extent of damage is below the functional threshold. However they’re still capable of spreading the infection eg asymptomatic COVID cases or Typhoid Mary.

Disease and viral factors which promote transmission include stability of the virion in the environment, transfer of virus into transmissible aerosols/secretions, asymptomatic transmission and ineffectiveness of immune system to control reoccurrence.

Mechanisms of viral transmission, ranked from lowest viral fragility to highest, include aerosols, food and water, fomites eg tissue/clothes, sexual/direct contact with bodily fluids, birth, blood transfusion/injection/organ transplant, zoonoses and genetic transmission. Naked viruses are much more resistant to the environment so are more likely to be respiratory and found in aerosols than enveloped viruses.

Risk factors for developing viral disease include age, health/nutrition/genetics, immune status, occupation (contact with agent/vector), travel history, lifestyle, sexual activity and contact with children. Older people have a weakened immune system and young children’s immune systems are naive meaning they’re more likely to be infected but they also tend to recover more quickly.