Mechanisms of Infection Flashcards
What are common routes of entry?
- mouth
- conjunctiva
- scratch, injury
- arthropod
- capillary
- skin
- anus
- urogenital tract
- alimentary tract
- respiratory tract
Viruses that initiate infection of skin, oral mucosa, genital tract, or eye
- poxviridae: minor abrasions or arthropod
- rhabdoviridae: biological, bite of vertebrate
- herpesviridae: genital tract
- adenoviridae: conjunctiva
Viruses that initiate infection of respiratory tract
- producing respiratory disease: adenoviridae, herpesviridae
- producing systemic disease, without initial respiratory signs: parvoviridae
Viruses that initiate infection of intestinal tract
- producing diarrhea: coronaviridae, toroviridae
- producing systemic disease, without diarrhea: caliciviridae, picornaviridae
Mechanisms of spread in the body
- local spread on epithelial surfaces
- subepithelial invasion and lymphatic spread
- spread by the bloodstream (viremia)
Pox virus
- produce infection via the skin
- local subepithelial and lymphatic spread
Paramyxoviruses and influenza viruses
Do not invade subepithelial tissues!
- enter lymphatic and spread
Rotaviruses or coronaviruses
Do not invade subepithelial tissues
- enter lymphatic and spread
Skin
Not a very important route
- food and mouth disease, vesicular stomatitis, pox, herpes
Respiratory secretions
Most important route!
Saliva
Rabies and FIV
Feces
Poliovirus and rotaviruses
Genital secretions
Herpes and immunodeficiency viruses
Urine
Viruses that replicate in the kidney
- rinderpest, infectious canine hepatitis, food and mouth disease
Milk
Viruses replicate in the mammary gland (not important)
- caprine arthritis-encephalitis, tick borne flaviviruses
No shedding
Not all virus replication ends in shedding
- replicate in CNS
Persistent infections
Infections that persist for the life of the animal - episodes of clinical disease occur infrequently
- herpesviruses
- canine distemper virus
Why are persistent infections important?
Serve as source of infection for other animals (constant shedding)
- can be reactivated and cause recurrent acute episodes of disease
- lead to immunopathologic disease
- associated with neoplasms
What are 3 categories of persistent infections?
- latent
- chronic
- slow
Latent infections
Virus is not demonstrable except when reactivation occurs
Chronic infections
Virus always demonstrable and often shed
- disease may be absent, chronic, or develop late
Slow infections
Virus gradually increases during a very long preclinical phase
- leads to a slowly progressive lethal disease
Infectious bovine rhinotracheitis virus
Alphaherpesvirus
- viral genome persists latently in neurons (episome)
- when episome is reactivated, infectious virus is produced and moves down sensory nerves and reaches the nasal mucous membranes or the skin
- proliferation occurs in epithelial cells, with virus shedding
Episome
Similar to an extracellular plasmid
Foot and mouth disease
Virus persists in the pharynx in cattle, sheep, goats and other ruminants
- not all infected animals become carriers
- no correlation between antibody levels and carrier
- virus can be found in buffalo for up to 2 years after infection
Lymphocytic choriomenigitis in mice
Caused by arenavirus, transmitted via horizontally and in utero (vertical)
Vertical transmission
Offspring becomes infected
Immunological trolerance
In presence of virus but in absence of antibody
Immunological tolerance (incomplete)
The presence of virion IgG complement and the complex is infectious
Offspring of infected females develop __________
Immuological tolerance
Subacute spongiform viral encephalopathies
- scrapie in sheep and goats (in the US)
- Creutzfelt-Jakob Disease in humans
- bovine spongiform encephalopathy (mad-cow)
- chronic wasting disease in mule deer and elk
- transmissible mink encephalopathy
Prions
Proteinaceous infectious particles
- concentrate in brain and spinal cord (not in muscle, milk, and blood)
- resistant to steam sterilization and cooking
- cannot grow prions, have to collect from infectious tissues
Prions are _______ that concentrate in the tissues of CNS
Misfolded proteins
- protein persuades other proteins to copy it
- incubation time: 1.5-30 years
- no immune responses, no interferon
Canine distemper
Paramyxovirus
- acute systemic infection, majority of dogs recover completely within 1 month
- minority: recovered dogs harbor the virus in brain cells, where it replicates slowly and eventually produces old dog encephalitis
Unique properties of persistent viruses
- nonimmunogenic agents
- integrated genomes
- growth in protected sites
- antigenic variation
Noniummunogenic agents
Prions
- do not induce interferon
- no immune responses, so host can not restrict the replication and pathologic effects
- ex: subactue spongiform encephalopathies
Integrated genomes
Retroviruses whose proviral DNA is integrated are maintained indefinitely, from one generation to the next, as part of the genome of the host
- proviral DNA may be implicated in oncogenesis
Alphaherpeviruses
Avoid immune elimination by remaining within cells of the nervous system
- as episomal DNA in ganglion cells during the intervals between disease episodes
- as viral DNA, subviral particles, or virions within axons prior to acute recurrent episodes
Betaherpeviruses (cytomegalovirus) and gammaherperviruses
Avoid immune elimination by maintaining serial infection by cell to cell contact
Antigenic variation
Visna/Maedi and equine infectious anemia viruses (lentiviruses, retroviridae)
- avoid immune response of the host by antigenic drift (generate variants)
- variants may become more virulent
Modification of host defense mechanisms
- defective antibody response
- defective cell-mediated immunity
- growth in macrophages
Defective antibody response
- viruses that replicate in lymphoid tissue and macrophages induce non-neutralizing antibodies
- antibodies combine with viral antigens and virions in the serum to form immune complexes –> immune complex disease –> deposit complexes in renal glomeruli or other organs
Growth in macrophages
In chronic infections, the virus appears to grow mainly in reticuloendothelial tissue (especially macrophages)
- viruses in macrophages avoid host immune resposne
Defective cell mediated immunity
- immunosuppression by the causative virus
- immunological tolerance
- presence of virus-antibody complexes
- failure of immune lymphocytes to reach target cells
- decrease in the numbers of Th lymphocytes
Antiviral chemotherapy
- attachment of virion to cell receptor - receptor analog
- primary transcription - transcriptase inhibitor
- reverse transcription - AZT
- translation of viral mRNA into protein - interferons
- posttranslational cleavage of proteins - protease inhibitors
- replication of RNA viral genome - replicase inhibitors
