Exam 1 Flashcards
What is a virus?
It is a small collection of genetic code (DNA or RNA), surrounded by a protein coat.
- Need a host to replicate
- Often cause damage to host cells in the process
History of Virology
Small Pox
Lady Mary Wortley Montagu and Edward Jenner
- 16th century disease killed an estimated 400k Europeans
- Jenner and Mary scabs are collected from patients inoculated with cowpox (less virulent) and used to inoculate other patients to prevent small pox.
Louis Pasteur
Robert Koch
- French
- Father of science of microbiology
- Studied, made beer, wine, and cheese
- Rabies vaccine development
Robert Koch and Pasteur
- Jointly proposed the ‘germ theory’
- Kosh’s postulates (framework for investigating disease)
- The agent must be present in every case of the disease
- The agent must be isolated from the host and grown in vitro
- The disease must be reproduced when the pure cultivated agent is introduced into a healthy susceptible host
- The same agent must once again be recoverable from newly infected host
F.A.J. Loeffler and P. Frosh working in 1898 with Robert Koch
- Foot-and-mouth disease
- First virus of vertebrates discovery
Thomas Weller and Ferderick Robbins
-The tissue-culture technique
Rosalind Elise Franklin, James Watson, Francis Crick
- Model of DNA
- Structure of DNA
Other historical figures
- Shope: discovered swine influenza
- Salk and Sabin: developed polio vaccines in the 1950’s
- Johnson in 1965 discovered the parvovirus of cats
- Small pox declared eradicated in 1980
- Montagnier and colleagues discovered HIV in 1984
- Pederson with colleagues in 1987 discovered FIV
- Rinderpest declared eradicated globally in 2011
What are the three Ds?
- Death
- Discharge
- Diarrhea
Future: Always a threat of existing foreign animal disease (FAD) or new emerging viruses
-United Sates Department of Agriculture Animal and Plant Health Inspection Service
- July 2021: APHIS study white-tail-deer samples for SARS-Cov-2 for antibodies. Some are exposed, IL, NY, PA
- November 2021 APHIS Malaysia and African Horse Sickness (AHS)
- January 2022 APHIS confirmed highly pathogenic Eurasian H5 avian influenza (HPAI) in a wild American wigeon, SC.
- February 2022: HPAI in a commercial turkey flock, IN.
- February 2022: expansion of wild bird surveillance for avian influenza
-June 2021: New effort called Flock Defender.
**up to 75% of emerging infectious diseases in humans can also impact the health of animals
**Understanding of viruses, their epidemiology and their control/prevention has been revolutionized by molecular studies.
Chicago area in 2015 and Canine Influenza
- High fever 103F
- Lethargy
- Cough
- Runny nose
Virology
- Preventative medicine (vaccines)
- Treatment is generally palliative (no anti-viral drugs)
- Strategy is to control through vaccination and biosecurity
- Rapid and reliable diagnosis is critical
- Know they industry you are serving
Classification and Replication of Viruses
- Can only replicate in living cells of animals plants and bacteria
- They are obligate parasites
- Metabolically inert when they are outside the host
- Rely on metabolic process of host to replicate
- Some have affinity to particular cell types
- Cannot capture and store free energy
- Efficient and economic
- Origin is uncertain, no fossil forms found
- Have a genome ability to adapt
Properties of viruses
- Heat sensitivity: denaturation, enveloped viruses more susceptible
- pH sensitivity: extremes are destructive
- Lipid solvents
- Chemicals: react with amino acids of proteins, some inactivate DNA or RNA
- Radiation and Ultraviolet light
- Humidity: different viruses respond differently
Virus structure and taxonomy
- Capsid (made of capsomeres glycoproteins) and envelop (some)
- Genome: DNA or RNA
- Viral proteins are lock and key to host cell receptors, initiating infection
- Both capsid and the envelop are antigenic
Taxonomy
Based upon
- Morphology of virion, capsid, and envelope
- Genome: DNA, RNA, ss, ds, etc
- Serological relationship (serotypes)
- Replication strategy
Class I: dsDNA ClassII: ssDNA Class III: dsRNA Class IV: +ssRNA Class V: -ssRNA Class VI: ssRNA-RT Class VII: dsDNA-RT
Retroviruses: ability to synthesize DNA from RNA with a unique enzyme
RNA viruses can have a segmented genome.
- Herpesviridae dsDNA = creeping
- Coronaviridae, ssRNA+, Corona = crown
- Picorna = small rna
- Retroviridae, ssRNA-RT Retro = backwards
- Rhabdoviridae, ssRNA -, bullet shape
- Parvoviridae, ssDNA
Symmetry
- Isometric (Icosahedral): 20 equilateral triangular faces. Ex: herpes viruses
- Helical: tubular construction with subunits arranged around the nucleic acid in a coil. Ex: rabies
No symmetry
- Complex: smallpox virus
- Filamentous: ebola virus (long snake-shaped)
Viral structure, DIVA principle
-Nucleic acid core
-Capsid: protein, protects genome. DETECTION of host’s cell receptor and binding
-Outer envelope
-Physical damage
-Chemical damage: UV radiation leads to chemical modification
-Enzymatic damage: nucleases released by host
*Herpesvirus: fragile
*Parvovirus: persistent in environment
-Viral capsid: capsomeres crystalized for receptor binding studying
Structural: important for viral stability
Non-structural: enzymes involve in viral replication
*Antibodies are generally formed against structural proteins
DIVA PRINCIPLE
*Antibodies formed against non-structural proteins helps differentiate animals vaccinated with inactivated vaccines from naturally infected
Promiscuous and Plastic
Promiscuous: having or characterized by many transient sexual relationships.
*Capable of infecting several species
Plastic: exhibiting adaptability to change or variety in the environment (influenza virus)
SARS-Cov-2
- ACE 2: Angiotensin Converting Enzyme 2, thought to be essential Negative Regulator of the renin-angiotensin system (RAS) essential for cardiac function and blood pressure control. ACE2R is situated in many organs of the body (lungs, brain, endothelium, heart, enterocytes etc)
- Spike protein (s): mediates the virus entry into host cell and binds to ACE 2 receptor.
Groups, serotypes, strains, and isolates
- Strain: is a well characterized virus
- Virulence: the ability to cause damage to the host specific to each strain
- Isolate: refers to the virus recovered from a specific host or location
- Serotype: generally means that immunity is not conferred by previous exposure to a different type (Foot-and-mouth disease). (Sero) types 1-26. Group specific antigen
Taxonomy basic rules
- Order (virales)
- Family (viridae)
- Subfamily (virinae)
- Genera (virus)
- Common names (no italics)
Important to recognize where the disease of interest is classified, family and genus, allows prediction of viral characteristics, similarly of disease, transmission and diagnosis.
Ex: measles and canine distemper same genus, clue of how to control it
Grouped by the disease they cause
-Enteric viruses: usually ingestion feco-oral route. Ex:
Picornaviridae, Parvoviridae, Adenoviridae.
-Respiratory viruses: inhalation respiratory transmission
Coronaviridae, Paramyxoviridae, Adenoviridae.
-Arboviruses: arthropod-borne, blood-feeding.
Rhabdoviridae, Flaviviridae, Orbivirus
-Oncogenic viruses: close contact, fomites, sexual contact. Ex:
Papovaviridae, Herpesviridae
Replication of viruses
Cytopathic effects in cell culture
- Knowledge of replication for a particular family of viruses is also helpful to the development of antiviral drugs.
- Viruses and cells have receptors and an affinity (complementary) that results in attachment
- Virus are highly specific in attachment sites, but others may have a wide host range.
Cytopathic effects
Cell transformation can occur
1. where cells pile up losing the property of cell inhibition = form giant cells or
2. Form occlusions in the cytoplasm or nucleus
3. Die
Giant cells: syncytia (come together)
- Herpes virus (Bovine herpes mammillitis),canine distemper virus (Paramyxovirus)
- New Castle disease- poultry: many cytoplasmic inclusions
**Not all viruses are Cytopathic
Summary of other types of virus cell integration
- Cytocidal: inhibition of DNA synthesis, cell death. Enteroviruses, reoviruses
- Persistent, productive: no cytophatic, continue to divide. Rabies, pestiviruses, most retroviruses.
- Persisten non-productive: Usually nil. Canine distemper virus in brain
- Transformation: Produce tumors when transplanted to experimental animals. Sarcoma viruses, polyoma virus (genital warts)
Calculating virus infectivity
In 1930’s embryonated egg was used
In 1950’s cell cultures have been used
*First influenza vaccine
Still used for isolating viruses
Quantitative Assays of Viruses
-Plaque Assay: dilution that calculates virus concentration.
-Tissue culture infective dose 50
Virus titer of 5x10^6 TCID50/ml
Pathogenesis: the manner of development of a disease
- Exposure without infection
- Subclinical infection
- Mild disease
- Moderate disease
- Severe disease
- Death of animal
- Infection is not synonymous with disease
- Pathogenicity: is the ability of the virus to cause disease
- Virulence is a relative measure of pathogenicity (e.g., strain A is more virulent than strain B)
- Virulence and pathogenicity are unrelated to infectivity and transmissibility
SEROTYPE: generally means the antibodies it produces
Viral Exposure/Infection
The outcome depends on
- Method of transmission
- Number of infecting particles (dose)
- Virulence of infecting particles
- Speed of viral replication and spread
- Degree of cellular damage
- Effectiveness of host defenses
- *Acute clinical disease
- *Subclinical disease (inapparent infection)
- *Induction of cancer
- *Induction of chronic progressive disease, especially of the CNS
Effects of viruses on the host animal
- Direct damage to cells due to cell death/apoptosis (according to location): paralysis, immune deficiency
- Disruption of normal cell functions: protein synthesis, secretions, membrane trafficking.
- Immune response to virus infected cell
- Immune cell release of cytokines
- Virus hijacking/expressing host genes
Host factors
- Outcome of the virus-host encounter is the product of the virulence of the infecting virus and the susceptibility of the host
- “interplay” between genomes influenced by environment
- Genetic: species, breed, organ/tissue
- Age: neonate vs. geriatric
- Hormonal influence: pregnancy
- Healthy living conditions
- Concurrent or mixed infections
- Exposure to vectors
- Immunity (innate/passive): intact membrane barriers, nursing, interferons, phagocytosis. Acquired: previous exposure, vaccination.
Obligatory Steps in viral infections
- Entry into host and primary viral replication
- Local or general spread, cell and tissue tropism, and secondary viral replication
- Evasion of host inflammatory and immune responses
- Shedding from host
- Cause damage to host
Tropism
Certain viruses have evolved to preferentially target certain hosts, tissues or cell types. Examples:
- Rabies virus: neurotropic
- Malignant catarrhal fever: vascular system
- Bovine virus diarrhea: lymphoid tissue
Cellular tropism: HIV and macrophages
Tissue tropism: influenza virus and lung tissue
Host tropism: Myxoma virus only infect rabbits and not humans
Rabies Neurotropic, toward CNS
- Direct inoculation
- Replicates at primary site
- Tropism-spread to secondary site where its choice cell target cell is CNS
- Systematic disease occurs
- Shed in secretions
- *If restricted to local, then no neurotropic
Herpesvirus moves away from CNS
- Direct inoculation
- Replicate at primary site
- Tropism-spread to secondary site, preferred cell.
- Systematic disease usually occurs
- Shed in secretions
- Epithelium, nerves dormant.
Enteric virus-Gastrointestinal tract, Intestinal Epithelium
- Parvo prefers crypt cells (stem cells) where active mitosis is going on. These cells move to the top to become goblet, enterocytes, etc.
- Rotavirus/Coronavirus: prefers villus, non-replicating cells.
Respiratory Tract-viruses
- Picornavirus: likes upper cooler tract (35C)
- Paramyxovirus & Influenza: like lower, warmer tract 38C.
Immune system cell viruses -Retroviruses (RNA viruses)
- FIV: targets T-cells, latent and active stage.
- HIV:
- BVDV: Lymphoid system. Transient infection to fetus (75 days), poor doer, recognized as self and no immune response mounted.
Principal types of infection
-LOCALIZED: limited to site of viral entry. Example:
Skin warts cause by Papillomaviruses.
Respiratory tract local: orthomyxoviruses cause influlenza, rhinoviruses cause “colds” in humans.
Alimentary tract: entero-, reo-, adeno-, rota-, corona-, and parvoviruses replicate only in GI tract, gastroenteritis.
- SYSTEMATIC: spreads to various organ systems depending on viral tropism. Ex: Canine Distemper.
- Paramyxoviruses
- Rotaviruses
- Papillomaviruses
Variations on the theme of localized and systematic
- Inapparent infections
- Immunopathologic disease: Feline infectious Peritonitis
- Congenital infections: Feline Panleukopenia
- Persistent and latent infection: Bovine Rhinotracheitis
- Slow virus infections occur where the incubation period is prolonged: FIV (feline immunodeficiency virus infection.
- Oncogenicity (Cancer): Feline Leukemia
- Herpes stays forever
Variations: Congenital Infections
- Viral infections during pregnancy: infection in utero, during birth, congenital defects, fetal death.
- Virus is usually transferred to the fetus during the viremic phase of the dam. Can result in persistent infections (BVDV PI calf, smaller brain w/ tumor).
- Reproductive failure, abortions, and teratogenic defects may result.
Influences:
-The stage of gestation at time of infection, transmission to fetus, ability to cause fetal damage. Examples:
Hog cholera, BVDV, bluetongue, feline panleukopenia, etc.
