Lecture 8: Virus Flashcards
What is a virus?
Contains…
Role of virion
Small infectious obligate intracellular parasite
Contains either DNA or
RNA genome which is surrounded by a protective, virus coded protein coat
The virion’s roles is to deliver its DNA or RNA into host cell
Classification of virus: Grouped based on…
1.Size and shape e.g. helical, Icosahedral
2.Chemical composition and structure of the genome e.g. RNA or DNA, single stranded (ss) or double stranded (ds)
3.Mode of replication; lytic and lysogenic cycle
4 Types of viruses description and example and drawing (contains what type of DNA)
- Helical
Tobacco mosaic virus
-infects a number of plants, slinky shaped capsid that twists around and encloses the RNA
2.Polyhedral
-Adenovirus
Causes pink eye to pneumonia. Composed of genetic material (DNA) surrounded by a many sided capsid (20 triangles per face)
3.Spherical
-Coronavirus
Helical viruses enclosed with a lipid envelope spiked with sugary proteins that assist in sticking to host cells. RNA
4.Complex Virus
-Bacteriophages
Infect and kill bacteria, resemble lunar lander with a head, tail sheath, tail fibres that attach to a cell membrane to transfer DNA material
Why does RNA have higher mutation rates?
Because of the error rate of the enzymes involved in RNA replication, these viruses usually show much higher mutation rates than do the DNA viruses
Single and double stranded RNA: Single strand extensions
Single stranded can be Sense strand or antisense
Sense – can function as mRNA
Antisense – cannot produce viral components
DNA virus:
Typicallu contains what DNA (ss or ds)
Stable?
Most DNA viruses contain a single genome of linear dsDNA
Relative stability of DNA allows for genomes much larger than possible forRNA viruses
why does RNA have more mutations compared to DNA?
RNA virus replication (unlike all other cells and DNA viruses) generally does not have an error correction ability
lack of proofreading ability in RNA polymerases
Mutations: antigenic shift and antigenic drift process
lecture slide
Transmission - portals of exits
- Fluids
eg: Water or human fluids (semen, blood, urine)
Measles, ruberlla, HepB and STD’s
2.Food
eg: Food prep, storage and handling
Salomonella, Hep A, tapeworm
3.Flies
Via vectors (ticks, lice, mozzys, flies)
Malaria, Lyme Disease
4.Fingers
Healthcare workers (dentists, nurses, doctors)
UTI, herpes, wound infections
- Fomites
Inanimate objects which carry pathogenic micro organisms on their surface
Equipmet, instruments, linen, toilet seat
MRSA transmission - faeces
Potential pathogen excreted in bowel, contaminate water supply, storm water run off.
Hep A, typhoid, worms, cholera
Portal of entry examples
Most viruses interact with the hosts epithelium cells
Can be bypassed when the virus is delivered to internal sites through penetration of the skin, eg: insect or animal bite
Transplantation of a virally infected organ
Cross the placenta to a foetus
Transmitted to a child during or after birth
Portal and examples of viruses that use the portal
Resp tract
GI tract
Gential tract
Skin
1. Direct contact
2.Penetration
Through placenta
Eye
Transplants
1. Solid organ
2.Blood
Resp tract:
Measles, mumps, rubella, Influ A, Influ B
GI tract
Hep A, Hep E, Poliovirus, rotovirus
Gential tract
HIV, Hep B, Hep C, HPV
Skin
Direct contact: HPV
Penetration: Injections (Hep C, Hep B, HIV
Mozzy: yellow fever virus
Ticks: heartland virus
Placenta: Measles, rubella, zika virus
Eye :Measles, rubella, adenovirus
Transplants
Organs: Hep C, Hep B, rabies
Blood, Hep C, Hep B, ebola
Mode of transmission
Direct and indirect types
Direct contact
Person-to-person transmission - touching, biting, kissing, or sexual intercourse
Expelled from the body - coughing, sneezing or talking
Vertical
Transplant
Indirect contact
Vehicle-borne
Vector-borne contact
What determines susceptibility to virus infection
1.Determined by the complex patient-virus interaction
2.Host genetic and metabolic background can significantly influence the outcome of a viral infection
3.Multiple innate factors (e.g., age, nutritional status, genetics, immune competency, and pre-existing chronic diseases) and external variables (e.g., concurrent drug therapy)
Why are some people asymptomatic
1.T cell memory
-the T cells in 40% to 60% of the donated uninfected bloods appeared to recognize the new coronavirus
- partial immunity could come from exposure to other coronaviruses, such as those that cause the common cold
2.Immunity from childhood vaccinations
They found that seven types of childhood were associated with having a lower infection rate from the coronavirus
This was especially true among people who recently received a pneumonia vaccine, which was associated with a 28% reduction in coronavirus-infection risk, and polio vaccines, which were associated with a 43% reduction in coronavirus-infection risk.
3.Biology
ACE2 receptors may affect the severity of illness a person develops from the new coronavirus. minimizing those receptors may obstruct the virus’ ability to replicate
Mechanisms of spread in the body
1.Local spread in the Epithelia
-Replication
-produce localised or spreading infection,
-infection spreads by infecting neighbouring cells
2.Sub epithelial and Lymphatic spread:
-exposed to Macrophages
-enter the lymphatics
-Inflammatory response
-tissue damage
-I/R
- Spread by the blood stream (viremia)
Via the lymphatic system
Viral Replication steps and diagram labelled
Viral replication involves six steps:
Attachment
Penetration
Un-coating
Replication
Assembly
Release
Diagram steps:
1. Virus enters the host cell and is uncoated, releasing viral DNA and capsid proteins
2.Host enzymes replicate the viral genome
3.Meanwhile host enzymes transcribe the viral genome into mRNA which other host enzymes use to make more viral proteins
4.Viral genomes and capsid proteins self assemble into new viral particles and exit the cell
Describe the lytic and lysogenic cycle
In the lytic cycle, the virus attaches to the host cell and injects its DNA. Using the host’s cellular metabolism, the viral DNA begins to replicate and form proteins. Then fully formed viruses assemble. These viruses break, or lyse, the cell and spread to other cells to continue the cycle.
The lysogenic cycle the virus attaches to the host cell and injects its DNA. From there, the viral DNA gets incorporated into the host’s DNA and the host’s cells. Each time the host’s cells go through replication, the virus’s DNA gets replicated as well, spreading its genetic information throughout the host without having to lyse the infected cells
Innate Immune response involves:
Interferon (IFNs)
Pro-inflammatory cytokines
Chemokines
Virus infected cells targeted by immune cells, which mediates viral clearance
Interferons: What are the types and expressed by what cells
Purpose of interferons? What do they promote
Combat virus infection
Modulate antiviral immune response
Secreted from infected cells and activate innate immune response
that
= promotes cytokine production, natural killer cell functions and antigen presentation
Three types of IFN;type Iand type II, Type III
type I and III IFNs are expressed by both immune and tissue specific cells
While type II IFN is specific for immune cells, including natural killer (NK) cells, CD4+T helper 1 (TH1) cells and CD8+cytotoxic T cells.
Draw the innate immune response to virally infected cells with IFN
Lecture Slide
Role of NKC:
Provide protection through…
How do they Act directly
How do they act indirectly
Provide antiviral protection through:
1. surveillance of danger signals
2. downregulation of MHC class I molecules ‘missing-self’
3. upregulation of MHC class I homologues ‘induced-self’ ligands
4.direct recognition of PAMPS
Act directly
1. kill without prior sensitization via the release of granzyme and perforin-containing cytotoxic granules
2.Produce cytokines such as interferon-c (IFN-c), which can limit viral replication
indirectly:
1.influencing the activation and/or trafficking of other key immune cell populations including dendritic cells (DCs) and T cells.
Dendritic Cells process in Innate immune system: Describe the diagram
Following the uptake of viral antigen, myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) migrate to lymphoid tissue to prime naive CD4+ T cells and CD8+ T cells.
Activated DCs produce a range of cytokines, such as interferon type 1, interleukin-12 (IL-12) and IL-15, which in turn activate natural killer (NK) cells and influence T cell survival and differentiation.
Depending on the cytokine signal, CD4+ T cells differentiate into T helper 1 (TH1) or TH2 cells (dashed arrows).
If CD4+ releases IL-12, there is differenation into TH1 cells, if IL-4 and 10 is secreted then it differeniates into TH2 cells.
TH1 cell-mediated IFN-y secretion stimulates the activation of cytotoxic T lymphocytes (CTLs) and the production of immunoglobulin G2a antibodies by B cells.
TH2 cell-mediated production fo IL-4 and 5 stimulates B cells to make immunoglobulin G1 antibody but also inhibits activation of TH1 cells.
T-cells role in adaptive immune response
Adaptive immune response
Initiates during first exposure
Simulates B cells to secrete antibodies
Protects from re-infection
During that first exposure, T helper cells sense the presence of one or more proteins (i.e., antigens) on the surface of the invading pathogen and release a variety of signals that ultimately stimulate B cells to secrete antibodies to those antigens OR release molecules to stimulate cytotoxic T cells to directly kill infected target cells
Antibody-independent B cell functions in viral infections
- Maintance of innate immunity by LT-ab
- Produce pro-inflam cytokines
3.Suppress T-cell immunity through IL-10
4.Present viral antigen to T-cells - Lysis of infected cells via granyzmes B
6.Stimulate B-cells via TLR
Viral escape mechanisms (5)
1.Inhibit every step of the innate and adaptive immune responses
2.Modifying the ligands of receptors to avoid detection - pattern recognition receptors, T cell receptors and antibodies
3.Inhibiting recognition by T cells by targeting antigen processing and presentation by MHC molecules
4.Prevent the efficient development of an immune response mimicking or blocking Interferons, cytokines and chemokines by viral proteins
5.Enter latency and remain dormant inside the cell, remaining undetectable
2 escape mechanisms specific to RNA and 2 escape mechanisms specific for DNA
RNA:
Speed – T cell exhaustion
Shape changing – mutation
DNA:
Camouflaging - change their antigenic determinants
Sabotage - interference with the action of host cellular proteins that are important components of the immune response.
Viruses that persist and cause chronic disease
HIV
Never eliminated
Integrates into the genome and evades he I/S
destruction of CD4+ T cells
HCV
causes chronic lesions in ~85% of infected individuals
Viral clearance is mediated by T cells, and this causes hepatocyte destruction and mild hepatitis
