Week 13 - Virology Flashcards
General Properties of Viruses
Obligate intracellular parasite - replicate within host cell only - unable to grow on synthetic media Host specific Size 10-300 nm Genetic material either DNA or RNA
Viral Proteins
Structural - make up viral structure - capsid made up of capsomeres - facilitate entry into host cells - protect viral nucleic acid Non-structural - coded for in viral genome - not part of virion however can be packaged in virion - contains enzymes needed for replication
Icosahedral and Helical Viral Symmetry
Icosahedral (cubic)
- solid regular sides
- 20 equal triangular sides
- greatest number of capsomeres packed in regular fashion
- all DNA animal viruses except poxvirus
Helical
- spiral structure
- capsomeres arranged in stair case fashion
- always contained within lipoprotein envelope
- glycoprotein spikes through lipid layer connected to underlying protein by matrix protein
- ssRNA viruses: influenzae, rabies
Baltimore Scheme Classification of Viruses
Class 1 - dsDNA
Class 2 - ssDNA
Class 3 - ds segmented RNA
Class 4 - ssRNA, positive
sense
Class 5 - ssRNA, negative
sense
Class 6 - ss RNA positive sense with ds DNA
intermediate before replication (retroviruses)
Class 7 - ds DNA with positive sense, part ss DNA,
with ss RNA intermediate (reversiviruses)
Main steps of Viral Replication
Attachment - to host cell via specific receptor on cell membrane Penetration - entry into host cell - sheds protein shell Replication of Viral Genome - production of mRNA - production of early viral proteins Production of late viral proteins Assembly of progeny virions Release of virions from cell (budding or lysis)
Bacteriophage different Life Cycles
Lytic (virulent)
- release of viral particles via host cell lysis
- lysis and death of host cell
Lysogenic (temperate)
- no lysis or death of host cell
- integration of viral genome onto host chromosome
- may enter lytic cycle
What are the two ways viruses can cause disease?
- Replication within the host cell leading to direct
damage of the cell - Host defenses leads to cell damage as it attempt to
clear the virus infected cells
CPE - Syncytia
Cell fusion
Certain viruses produce specified fusion proteins which mediate entry into cell
Also cause plasma membrane
Formation of giant multinucleated cells (Syncytia)
CPE - Inclusion Bodies
Bodies that appear in cells as a result of viral infection
They are:
- an aggregation of mature viral particles
- altered staining patterns at sights of virus synthesis
- degenerative changes due to infection
CPE - Transformation
Some viruses produce cancerous or pre-cancerous like changes
These viruses may act together with other cellular proteins and can cause mutations
What is Cytopathic Effect (CPE)
The effect of virus replication in the host cell
Cytokines and the Cytokine Storm
Cytokines released by immune system in response to viral infection
Attract T cells and macrophages
Controlled by feedback loop
Cytokine storm is the sudden outpour of various cytokines in response to viral infection
Feedback loop uncontrolled and results in tissue damage
HIV
Causes depression of immune response by destroying helper T-cells
Destruction of adaptive immune response
Causes opportunistic infections and tumors
Types of Skin Rashes
Vesicular Eruptions - replication of virus and direct damage to epithelial cell (Herpes)
Maculopapular Rash - due to destruction of virus infected cells by cytotoxic T-cells (Measles)
Purpuric Rashes - associated with fall of platelets due to viral infection (Rubella)
Hemorrhagic Rashes - due to disseminated intravascular coagulation resulting from viral infection (Dengue)
How do viruses evade the immune response?
Some viruses:
- don’t display enough antigen on cell surface
- inactivate B cells, T cells and macrophages
- interfere with expression of MHC proteins
Acute non-persistent, Persistent and Latent Infections
Acute
- usually self limiting and will resolve without intervention
Persistent
- infection not terminated by immune response
- persistence of viral DNA in host
Latent
- some never cause disease
- during latent phase infections sub clinical
- some reactive causing episode of illness
Insidious Infection
Prion diseases
- abnormally protein configuration
- can occur during spontaneous mutations
- abnormal protein contacts normal protein and will convert to abnormal conformation (recruitment)
- fatal
Herpes Virus
Group 1 - dsDNA
Icosahedral
Replicates in nucleus of host cells
Enveloped - phospholipid rich with viral glycoproteins for cell attachment
Form latent infections which may reactivate at later stage
HSV Entry
Attachment via envelope glycoproteins
- triggers fusion of viral envelope of cell
Nucleocapsid enters cytoplasm
Goes to nucleus and viral DNA released
HSV Gene Expression
VP16 protein in tegument activates alpha phase genes
Needs to bind to host Oct1 and HCF which are cellular proteins
Genes expressed in phases
alpha - immediate early, regulators of gene expression
beta - early, proteins for DNA replication
gamma - late, structural proteins
One phase activates the next, inhibits the previous phase
Assembly in nucleus
Released through ER
HSV Latency
Activation of HSV genes in neurons is limited
- failure to express alpha genes
Reasons why failure to express alpha genes in neurons:
1. Latency Associated Transcripts
- short RNA fragments from virus that interfere with alpha genes
2. VP16 fails because HCF is cytoplasmic in sensory neurons
Influenza Virus
Class 5 - ss(-)RNA segmented genome
Enveloped
Helical
Has surface peptides haemagglutinin and neuraminidase
Influenza Infection Process
Binding to cell
- haemagglutinin on surface of virion
- binds sialic acid residues on mucous membrane
- also causes fusion and entry
Release of Viral Genome
- M2 protein forms channel allowing H+ ions to enter
- low pH weakens M1 (matrix protein) bond to release nucleocapsid
Each segment of RNA is bound to nucleocapsid protein (NP) which transports it to nucleus
Influenza Replication
Occurs in nucleus
After transporting to nucleus
- negative RNA is template for + RNA which is mRNA
- mRNA sent to cytoplasm for translation
- progeny nucleocapsid sent to cytoplasm where assembly occurs at plasma membrane
- neuraminidase releases virions
