PID Virology Flashcards
The single biggest threat to man’s continued dominance on the planet is?
Viruses
characteristics of a virus are?
Viruses are non-living entities.
- Viruses contain nucleic acid genome (DNA or RNA) surrounded by a protein coat and, in some cases, other layers of material, such as a lipid envelope.
- Viruses do not possess standard cellular organelles such as mitochondria, chloroplasts, Golgi, and endoplasmic reticulum with associated ribosomes.
- Viruses cannot make energy or proteins by themselves and have to rely on a host cell.
- All Viruses are obligate intracellular parasites. Outside the living cell, viruses are inert or dormant particles, whereas, inside the cell, the virus hijacks and utilizes the host cell machinery to produce its proteins and nucleic acid for the next generation of virus.
- Viruses do not have the genetic capability to multiply by division. The process of Virus reproduction resembles an assembly line in which various parts of the virus come together from different parts of the host cell to form new virus particles.
the smallest virus is
the parvo virus (18-28nm)
Virion vs Virus
- Virion: A complete virus particle that consists of an RNA or DNA core with a protein coat sometimes with external envelopes and that is the extracellular infective form of a virus.
- Virus: is a broad general terminology used to describe any aspect of the infectious agent and includes: the infectious (Virion) or inactivated virus particle, or viral nucleic acid and protein in the infected cell.
what is a viroid
Viroid: An infectious particle smaller than any of the known viruses, an agent of certain plant diseases. The particle consists only of an extremely small circular RNA (ribonucleic acid) molecule, lacking the protein coat of a virus.
Edward Jenner did what?
he inoculated some “cowpox matter” (probably infected pus) repeatedly into arms of a healthy 8 year boy who became immune and did not succumb to small pox. Vaccination –derived from the Latin word ‘vacca” meaning “cow” – had been invented.
Louis Pasteur did what?
injected dried, potassium hydroxide treated, infected rabbit brain material in two boys bitten by rabid dogs and both of them recovered.
what is the strx and composition?
A capsid is the protein shell of a Virus. Capsid is usually symmetrical
A capsomer is the basic subunit protein in the capsid of a virus.
Capsid + Virus Nucleic acid (DNA or RNA)/Genome = Nucleocapsid
Some Viruses may have an envelope, which is usually a lipid bilayer with embedded proteins. The envelope facilitates virus entry into host cells and may also help the virus to evade the host immune system.
Glycoproteins on the surface of the envelope serve to identify and bind to host cell surface (cell membrane) and are also significant to host immunity.
6 shapes of viruses
Tadpole-shaped Bullet-shaped Filament-shaped Rod-shaped Brick-shaped Spherical
Pleomorphism is
the ability of some Virus to alter their shape or size
Some Virions also contain Enzymes critical to Infection what are they?
Lysins: Hydrolytic enzymes produced by bacteriophages to cleave the host’s cell wall.
Retroviral integrase (IN): Enzyme produced by a retrovirus (such as HIV) that enables its genetic material to be integrated into the DNA of the infected cell.
Reverse transcriptase (RT): Enzyme used to generate complementary DNA (cDNA) from a RNA template.
Nucleic acid polymerases: Viral Genome Replication.
Neuraminidases: Enzymes that cleave glycosidic bonds. Allows release of viruses from host cell
what are the steps of viral replication?
- Attachment
- Penetration
- Uncoating
- Synthesis of Viral Nucleic acid and Protein
- Assembly and Maturation
- Release in Large Numbers
one-step viral growth curve
- viral adsorption and entry
- viral uncoating and replication (eclipse period)
- viral maturation
- viral release (Burst)
(2 & 3 = latent period)
the hight of the growth curve represents what?
the # of virions released after maturation
the fastest replicating virus is?
the slowest replication virus is?
(measured by the # of particles / host cell / hr)
fastest is Picornavirus
slowest is retrovirus
viral Attachment to Host Cell Surface is mediated by?
Mediated by interactions between the Virus and Complimentary Receptor on Host Cell surface. Cell that lack the appropriate receptor escape being infected by viruses.
- In some cases, binding to a cellular receptor is not sufficient for infection: an additional cell surface molecule, or co-receptor, is required for entry.
viruses have evolved to use Host Cell Surface receptors, what are these receptors made of?
Receptors may be proteins, carbohydrates, glycoproteins, lipids, lipoproteins, or even complexes
viral uncoating is?
- Release of Viral Genome in Host Cell. Virion can no longer be detected; known as the “eclipse period”
- Some animal viruses begin to uncoat after binding to the external receptor, but are not completely uncoated until inside the cell (Poliovirus).
- Uncoating in some animal viruses requires a complex series of steps involving both host and viral gene products (Poxvirus).
- In some other viruses, such as retroviruses and reoviruses, the first stages of the viral replication cycle (transcription, replication) actually occur inside the capsid.
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Virus Nucleic Acid and Protein Synthesis
DNA VIRUS REPLICATION
DNA Viruses:
Replication of Viral DNA primarily occurs in host cell nucleus.
Capsid and other proteins are synthesized in host cell cytoplasm using host cell machinery.
Newly formed Viral proteins localize in the nucleus to combine with newly synthesized Viral DNA to form new Viral particles.
Pox Viruses are an exception, as they have been found to replicate in the cytoplasm of infected cells.
- Viruses with Small, Single-Stranded DNA Genomes (Parvovirus): Single-Stranded DNA genome double-stranded DNA mRNA Replication occurs in the nucleus
- Viruses with Large Double-Stranded DNA Genome (Herpesviridae) Complex Replication process. Encode additional proteins. These proteins can either be structural (capsid proteins, matrix proteins, envelope proteins, etc) or regulatory (transcription factors, polymerases, enzymes involved in nucleotide metabolism, etc)
Virus Nucleic Acid and Protein Synthesis
RNA VIRUS REPLICATION
RNA Viruses: Most replicate entirely in the cytoplasm of infected cells. Exceptions are orthomyxoviruses and retroviruses, where host cell nucleus is involved. (+) Strand Viruses: Synthesis of viral proteins (including replicase) from viral genomic RNA. (-) Strand Viruses: Synthesis of + strands using the virion associated polymerase. These + strands can either be full length or subgenomic mRNAs. Viruses with Double-Stranded RNA Genomes: Early transcription occurs in partially uncoated virions using Viral enzyme in host cell cytoplasm mRNA translated into protein final stages of viral replication and gene expression occur in newly formed Viral particles in host cell. Retroviruses: (+) sense Viral RNA cDNA integrated into host cell chromosome Reverse Transcriptase The host cell then treats the viral DNA as part of its own genome, translating and transcribing the viral genes.
VIRUS REPLICATION:
Assembly is:
Assembly of Virus Genome and Proteins into New Virions follow a Specific Order. May take place in Nucleus, Cytoplasm, or in Plasma Membrane (Most Enveloped Viruses).
possible impact on the host cell by a virus?
- Cell Death: Lysis
Alteration Cell Membrane
Apoptosis (Cell Suicide) - Transformation of Cell to Malignant one
- Fusion of Cells, Multinucleated (hybrids)
- No apparent changes to the infected cell. Latent, Persistent or Chronic infection
Virus Epidemiology and its Surveillance is?
.
- The study of the determinants, dynamics, and distribution of vital diseases in populations. Public Health
- The systematic collection, analysis, interpretation, and dissemination of data on Viral Diseases on an ongoing basis, to gain knowledge of the pattern of disease occurrence and potential in a community, in order to control and prevent disease in the community
Porcine Epidemic Diarrhea Virus (PEDV) what did/can it
cause economically?
causes severe Diarrhea and Vomiting in Pigs. First identified in the United States in May 2013. By the end of January of 2014, spread quickly across many US states, causing severe economic losses.
what is Molecular Epidemiology of Viruses
The use of molecular biological data as the basis of epidemiological investigation of Viral Diseases
The use of molecular biological data as the basis of epidemiological investigation of Viral Diseases is:
- Crucial information not only on general prevalence, but also on genetic diversity and origin of viruses. Important for designing or judging efficacy of vaccines, developing diagnostics, and for conclusive evidence for transmission of viruses from animals to humans (Zoonosis) or vice versa
possible ways of viral transmission are?
A. Direct-Contact Transmission: Direct physical contact with infected/Susceptible Host
B. Indirect-Contact
C. Common-Vehicle Transmission
Fecal contamination of Water or Food and Virus contamination of Meat or Meat products
Contaminated inanimate objects (Fomites)
D. Airborne Transmission
E. Vector (Arthropod)-Borne Transmission
Vertical Transmission is?
Infection that is transferred from Mother/dam to embryo, or fetus, or newborn before, during, or shortly after parturition
Enzootic Viral diseases (Endemic in humans) is?
The constant presence of a Viral disease within a given geographic area or population group.
Epizootic Viral diseases (Epidemic in humans) is:
The occurrence of more cases of Viral diseases than expected in a given area or among a specific group of people/animals over a particular period of time. Refers to peaks in disease incidence that exceed the endemic/ enzootic baseline or expected incidence of disease.
Diagnosis/Detection of Viruses/Viral Diseases
Diagnosis of Viral Infections by Gross Evaluation and Histopathology
- Clinical Signs
- Necropsy
- Histopathology
Detection of Viruses by Cultivation/Isolation
ELISA
(Enzyme-Linked ImmunoSorbent Assay)
- 3 TYPES OF ASSAY
Detection of Viral Antigen or Host Antibody against Virus
- Direct Assay
- Indirect Assay
- Capture Assay “sandwich”
Antiviral Drugs work by…
Interfere with the ability of a virus to infiltrate a target cell or target different stages of replication/Synthesis of components required for replication of the Virus.
Immune system stimulation for Tx
Interferons, class of proteins that has antiviral effects and modulate functions of the immune system.
Prevention and Control of Viruses by
A. Vaccination:
– Non-Replicating Virus Vaccines
- Vaccines Produced from Inactivated Whole Virions
–Vaccines Produced from Purified Native Viral Proteins
- Vaccines Produced by Recombinant DNA and Related Technologies
- Subunit Vaccines Produced by Expression of Viral Proteins in Eukaryotic (Yeast, Mammalian, Insect), Bacterial, or Plant Cells.
- Attenuation of Viruses by Gene Deletion or Mutation of Virus Genome
B. Proper Hygiene and Sanitation:
- Use of disinfectants. Disinfectants are chemical germicides formulated for use on inanimate surfaces.
- A doption of “all in, all out” management system, in which the animal houses are emptied, cleaned, and disinfected between batches of animals. No contact between different batches of animals.
- Frequent hand washing and decontamination of contaminated equipment are essential.
- Proper waste management in Farms
C. Eliminating Arthropod Vectors (Arthropods transmit many Viruses, such as Dengue, Chikungunya, West Nile, EEEV)
D. Quarantine & Culling
- To separate and restrict the movement of animals.
- Culling (killing) of Animals
- Proper Disposition of Culled Animals
Pathogenicity vs Pathogenesis
pathogenicity - refers to the ability of a Virus to cause Disease in Host (i.e., harm the host). The Virus which causes Disease is called a Pathogen.
- pathogenesis - is the manner/mechanism of development of a Disease.
The term Virulence is used as?
Avirulent is?
- a quantitative or relative measure of the degree of pathogenicity of the infecting virus
- Not Virulent (Not harmful to the host). Derived from the Latin word “Virulentus”, meaning “a poisoned wound” or “full of poison.”
Virulence is not an absolute property of a Virus, but depends on many variables the Factors related to Virus are?
- Genetic Variation of Virus
- Route of entry of Virus in Host
- Affinity of Virus to Host Organs
- Dose of Infection
Immuno evasion
Virulence is not an absolute property of a Virus, but depends on many variables are Factors related to Host are?
- Host Species
- Host Immunity
- Host Physiological factors (Nutrition status, Age, Hormonal Factors, Stage of Cell Differentiation)
- Fever
what is a way of quantifying a Measure of Virulence?
- Lethal dose 50 (LD50): The dose of the virus required to cause death in 50% of animals, such as mice.
- the lower the LD50 = more virulent the Dz
viruses cant penetrate intact skin so in this method of transmission it must enter via
a wound or broken skin
what must a Virus do/overcome to Spread in Host via a wound for entry?
A. From Local infection of Epithelial Surfaces
- Viruses may reach subepithelial layer/underlying tissues from epithelial surfaces.
To do this, Viruses should overcome local host defense.
B. To Subepithelial Invasion and Lymphatic Spread
- In subepithelial tissues, viruses get access to lymphatics, phagocytic cells and tissue fluids.
- These may help carry Virus to the Blood Stream.
C. To Blood Stream and Then spread via blood stream Viremia: Presence of virus in the blood
what is viremia?
primary viremia can happen by?
Secondary viremia can happen by?
Viremia: The presence of a virus in the blood.
Primary Viremia:
Initial entry of virus into the blood. Can happen in 2 ways:
1.Spread of virus infection to blood from subepithelial tissue/ lymphatics (refer previous slide)
2.Directly injected in blood, through bite of mosquitoes, or syringes
Secondary Viremia:
Virus has replicated/multiplied in major organs & once more entered the circulation.
Disseminated Infections are?
Infection spreads beyond the primary site of infection.
Systemic Infection:
If a number of organs or tissues are infected.
Neurotropic virus are?
Viruses that can infect neural cells. Infection may occur by neural or hematogenous spread.
Neuroinvasive virus are?
Viruses that enter the central nervous system (spinal cord and brain) after infection of a peripheral site.
Neurovirulent virus are?
Viruses that cause disease of nervous tissue, manifested by neurological symptoms and often death.
Tropism is?
The specificity/Affinity of a virus for a particular host tissue
Trojan Horse vehicle of infection
(Trafficking Monocytes Transport Viruses)
Viruses enter Monocyte –> Monocyte cross Blood–Tissue barrier (BBB) –>
Viruses come out of Monocyte in the CNS
Pantropic Viruses can?
Can Replicate in more than one host Organ/Tissue
- An enteric virus replicates in gut, but not in lungs.
- A respiratory virus replicates in lungs, but not in nerves.
what are the Mechanisms of Viral Injury and Disease
Virus–Cell Interactions
- Inhibition of Host-Cell Nucleic Acid Synthesis
- Inhibition of Host-Cell RNA Transcription
- Inhibition of Processing of Host-Cell Messenger RNAs
- Inhibition of Host-Cell Protein Synthesis
- Cytopathic Effects of “Toxic” Viral Proteins
- Interference with Cellular Membrane Function
what is the outcome for cells of Viral Injury
A. Cell lysis/bursting following virus replication allowing release of new viruses
B. Apoptosis is the process of programmed cell death, which is essentially a mechanism of cell suicide that the host activates as a last resort to eliminate viral factories before new virus production is complete.
- Different from Lysis where viral replication is complete, host cell is destroyed and new virions released.
C. Oncoviruses: Some Virus can cause cancer, and are known as oncoviruses or oncogenic viruses (papillomavirus, retrovirus)
D. Persistent Infection: Some viruses do not cause immediate death of infected host cells, but cause persistent infection. Many of these viruses remain latent or dormant in host cell for long periods, escaping detection by the host immune system . Some of these viruses also cause chronic stimulation of the immune system of host, resulting in immunopathology.
Virus Shedding: Shedding is Critical to virus because it allows?
thus it is done from?
.
transmission:
- infectious virions is crucial to the maintenance of infection in populations.
- (The amount of virus shed in an excretion or secretion is important in relation to disease transmission.)
- viruses are shed from a variety of sites and several sites.
Persistent infections can be shed at _____ titers over a ______ period of time
lower longer (months to years)
Acute infection: usually have _______ shedding over a _______ time period.
intensive
shorter
skin conditions caused by a virus can be visible.
name some.
- Warts caused by Papillomavirus -
- Nodules in Lumpy Skin Disease, Cattle
- Ulcers in FMD
- Erythema in Hog cholera
GI viruses can cause but are not limited to?
most but not all lead to :
Malabsorption, Diarrhea, Pronounced dehydration, Acidosis, Hemoconcentration -Blunting and fusion of intestinal villi - parvo, pestivirus
-Marked Villus Atrophy and Fusion.
pathogenic Respiratory tract viruses can cause:
Tropism for different parts of the respiratory tract with considerable overlap.
- Inflammation
- Exudation
- Influx of inflammatory cells
- Obstruction of air passages
- Hypoxia & Respiratory distress
- Secondary Bacterial Infection
pathogenic CNS pathogens can cause but is not limited to?
Lytic:(destruction/bursting) infections of neurons
- Neuronal necrosis (Necrosis is death of body tissue)
- Neuronophagia (killing/devouring of neuronal cells by phagocytic cells)
- Perivascular cuffing (Inflammatory cells around blood vessels in CNS)
- Progressive Demyelination (Canine Distemper)
- Neuronal vacuolation in Prion disease
pathogenic Viral Infection of the Hemopoietic System can cause but is not limited to?
-DIC
-Vasculitis (inflammation and damage to blood vessels) can be
mediated by Immune-Complex (antigen-antibody complex) formation. Seen in infection FIP.
Viral Infection of the Fetus that cause developmental defects of embryo or fetus after in-utero infection.
these viruses are called?
Teratogenic viruses
Note: Depends on species and gestational age.
Viral immuno-evasion strategies include?
name 7 ways
Negative cytokine regulation Alterations in antigen processing pathways Evasion of natural killer cells Alterations in the B cell system Alterations in the T cell system Viral evasion through latency Inhibition of Apoptosis
