Human Viruses
- Vaccine Preventable
- Measles
- Mumps
- Rubella
- Influenza
- Varicella-zoster
- Hepatitis A/B
- Rotavirus
- Rabies
- COVID
- Yellow Fever
- …list goes on
Virus Properties
- A virus is defined as a nucleoprotein complex that infects cells and uses their metabolic
processes to replicate - Smallest known infective agent (22-250 nm)
- Metabolically inert – no metabolic activity outside the host cell; must enter the host to
replicate - Most are highly species specific
Viral Key Concepts
- Obligate intracellular parasites
- Use host’s machinery to replicate
- Contain nucleic acid core with a protein capsid with or without a lipid envelope
- Single or double stranded RNA or DNA
- Most RNA viruses replicate in the cytoplasm
- Most DNA viruses replicate in the nucleus
- Assemble new virus particles within the host cell
viruses contain either single or double-stranded nucleic acid. So Rna or DNA, they can’t have both
Rna viruses mainly replicate in the cytoplasm of the host cell, whereas DNA viruses replicate in the nucleus and the only exception to that are pox viruses
Virus vs. Virion
- Virus is a broad general term for any aspect of the infectious agent
and includes: - the infectious or inactivated virus particle
- viral nucleic acid and protein in the infected cell
- Virion is the physical particle in the extra-cellular phase which is able
to spread to new host cells - complete intact virus particle
actual physical particle
that is able to spread to new host and infect new host,
that whole entire virus, containing all of its components, is referred to as the virion
Structure of viruses
The virion
Nucleocapsid
Genome
(nucleic acid)
Capsid
Capsomere
Envelope
Peplomers
(spikes/ligands)
viruses are often defined not only by their, you know, genome, whether they’re double stranded single-stranded Rna DNA, but also their Capsid structure,
There can be a envelope that’s derived from the infecting host cell. And outside of that envelope are these spikes, ligands from the virus that help interact with host cell receptors
Not all viruses are enveloped
Structure of a virus used for classification
genome
DNA/RNA
Double/single-stranded
Polarity (+/- sense)
Segmented (# of pieces)
Capsid Capsid symmetry (polyhedral/helical/complex)
Virion size
Envelope Enveloped/not
. For example, influenza viruses contain influenza. A and B contain 8 segments of their Rna genome within the capsule that’s enveloped.
and that’s important to understand why we see different strains of influenza circulating. Because there’s these different segments that can come together and create different sorts of species
we will classify viruses based on that caps of symmetry. So there’s 2 main ones.
Either polyhedral or helical
Basic Structure
- Nucleic Acid:
* DNA or RNA (never both!) - Capsid:
* Single or double protein shell composed of capsomers
* Capsid Symmetry: Icosahedral or helical - Envelope:
* Surrounds the nucleocapsid
* Virus-specific proteins plus lipids and carbohydrates
derived from the host cell membrane
Nucleic acid + Capsid = Nucleocapsid
Baltimore Classification
I DNA 2 Genome → mRNA Herpes viruses (HSV, VZV, CMV, EBV)
II DNA 1 Genome → dsDNA → mRNA Parvovirus
III RNA 2 Genome → mRNA Rotavirus
IV RNA 1 (+) Genome = mRNA Picornavirus
V RNA 1 (-) Genome → mRNA Rabies virus
VI RNA 1 (with reverse
transcriptase)
Genome + RT → DNA → incorporated
into host genome → mRNA HIV
VII DNA 2 (with reverse
transcriptase)
Genome → RNA intermediate → mRNA
DNA is replicated through an RNA intermediate; the RNA may
serve directly as mRNA or as a template to make mRNA
Hepatitis B virus (hepadnavirus)
Virus Taxonomy
- Viruses with similar structural, genomic & replication properties are
grouped into families (suffix: -viridae) - e.g. Herpesviridae
- Families subdivided into genera (suffix: -virus)
- e.g. Herpes Simplex Virus, Cytomegalovirus, Varicella Zoster Virus
- Subtypes based on nucleotide sequence and antigenic reactivities
- e.g. Herpes simplex virus type 1, Herpes simplex virus type 2
Viral Capsid Forms
helical
icosahedral
complex
Envelope
- Attachment
- Entry
- Assembly-matrix proteins
- Release
- Proteins are viral
- Lipids are host
- Rare in plants or bacteria
- If the membrane envelope
is destroyed, the virus
becomes noninfectious.
Enveloped viral budding
The envelope is derived actually from the host cell that infects, and i’ll show you guys some images in greater detail, and essentially once the virus is able to, when, as it buds out from the infecting from the host cell, that it is infecting as it buds out, it actually impregnates these viral proteins on the outside. So those spikes or glyco proteins, and that allows the next progeny of viral particle to infect neighoring hosts
Matilda was interested in what virus she was infected with.
She took an NP swab and looked at the specimen under the
EM. What can we tell from this?
- Assuming that Matilda was sick with influenza, would
it be more correct to say she was infected by a virus
or a virion? Why?
slide 25
Viral Replication
- Adsorption (attachment)
- Entry
- Uncoating
- Transcription
- Synthesis of virus components
- Assembly
- Release
Attachment and penetration
Viruses can enter
cells in three
different ways:
- Absorption
- Random collisions between virions and target cells
- Binding of viral proteins to receptors on host cell surface
- Virus particle or genome crosses host cell plasma membrane (3 strategies)
- Uncoating
- Removing all or part of the viral capsid
- Viral genome is accessible to host cell’s transcription and translation machinery
- Penetration and uncoating often occur in the same step
- Viruses can enter
cells in three
different ways: - Direct penetration
- Fusion
- Endocytosis
So you have non enveloped viruses, often directly penetrating the host cell through receptors on the side of plasma membrane that release the virus directly into the host cell, leaving its capsid on the outside.
You can have fusion and endocytosis which are important strategies for enveloped viruses. So
in the case of fusion, membrane, fusion, you have this envelope, the virus using it’s viral like your proteins binding to receptors on the host cell, the cytoplasm of membrane.
that envelope, then fuses with that cytoplasmic membrane merging into one and releasing that viral capsid
endocytosis is that host cell basically involving the virus, capsid and it’s envelope altogether. So you have binding of the viral particle through the glycoproteins and receptors. But instead of the envelope using with that Cytoplasm membrane, you have that Cytoplasm membrane of the hostel, engulfing that entire virus, disintegrating that envelope within, and releasing subsequently the capsule and the viral genome for replication.
Transcription, Translation and Synthesis
DNA viruses
- DNA viruses:
- replicate their DNA in host cell nucleus mediated by viral enzymes
- synthesize capsid and other proteins in cytoplasm using host cell enzymes
- new viral proteins move to nucleus where they
- combine with new DNA to form new viruses
- Exception - Poxviruses synthesize their parts in host cell’s cytoplasm
initially it needs to replicate its DNA within the host nucleus. Then it translates out into the cytoplasm, develops the rest of the capsule and puts the proteins together, and then it can be released from the host cell
Transcription, Translation and Synthesis
RNA viruses
- RNA viruses:
- (+) sense RNA acts as mRNA
- viral proteins are made immediately in
cytoplasm mediated by viral enzymes - naked nucleic acid is infectious
- (-) sense RNA
- e.g. influenza - 1
st makes a (+) sense RNA copy
via viral enzyme
Assembly of progeny viruses
- Replication of viral genome and synthesis of protein are complete
- Viral capsomers self-assemble into crystal-like arrays
- Newly formed capsid is filled with viral nucleic acid
How can a virus enter a host cell?
Three ways to enter:
1. Direct penetration
2. Fusion
3. Endocytosis
- Can a non-enveloped virus enter by fusion?
- No, a viral envelope is required to fuse with the host cell membrane
Clinical Diseases & Routes of
Transmission
Pathobiology of viral diseases
Interactions between virus and host = signs and symptoms of disease
- After encountering a host cell, the virus must:
- Enter the cells
- Undergo a period of primary replication
- Spread to its final target tissue
- Infect and successfully replicate in a susceptible
population of host cells
Types of viral infections
- Lytic
- Multiple rounds of replication results in death of the host cell (virus factory)
- Polio, Influenza
- Latent
- No immediate production of progeny virus
- Viral nucleic acid carried as extrachromosomal element or an integrated sequence in
the host cell DNA - Herpesvirus-1, retrovirus
- Chronic
- Virus particles continue to be shed after the period of acute illness has passed
- Slow release of virus particles without death of the host cell
- Hepatitis B
lytic viral infections have viruses that multiply in significant amounts, and cause the host cell to die. And once that host cell dies, it releases all the progeny
So once the virus gets into the host cell, it’s not necessarily
replicating right away. Sometimes it can be carried as an extra chromosomal element, or integrated into the host cell DNA
whatever reason stress immune suppression etc., will then cause kind of give that virus to replicate and infect other cells
continuing to shed even after the period of acute illness. So we have high virus viral loads being produced within the the body. But after that acute illness phase the virus is still producing it’s particles, and replicating in in very small amounts, without causing any deaths to that host cell
Outcome of viral infections
Adsorption (attachment)
Engtry
Replication Latency Transformation
Cell Fusion Release
once it attaches and enters the cell, it can replicate right away, causing acute illness
depending on the virus. It could cause other host cells to fuse, together with the release of other, with other viral components that cause some sort of abnormalities within the host cells.
The replication process of the virus itself can cause direct rlease. The host cell dies, and you have release of the progeny into into the host, and it can infect other cells some of the times
or it can cause often the case with some of these oncogenic viruses. Once it enters the cell, it just enters into a state of dormancy, and then, for whatever reason transforms the host cells into malignant or cancer cells
Virus-host cell interaction
- Cell death (Lytic)
* due to cytopathic effect of virus - Cell transformation
* cell converted to malignant or cancerous cell - Latent infection (Occult)
* persistent infection in quiescent state which may reactivate anytime to produce disease; continuous or intermittent shedding - Cell fusion to form multinucleated cells
diagram with drug targers
Highlights drug targets throught viral replciation process, starting from attachment, binding, replication
drugs that targets the surface subunit, preventing attachment altogether. You can also have inhibitors that target the host proteins directly, rather than the viral subunits and prevent bind attachment that way. You can have antivirals that target, the Rna dependent Rna Polymerase that’s used when you need to translate that negative sense, Rna, to a positive sense
you can have protease inhibitors. So these are antiviral drugs that target essentially the maturation and assembly portion of the the virus. Once nucleic acid has been replicated
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Public Health & the Canadian Immunization System18
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Immunology Overview and Discussion of the Types of Immunizing Agents31
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VACCINE PREVENTABLE DISEASES (PART 1)25
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VACCINE PREVENTABLE DISEASES (PART 1) CONT'D33
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Introduction to Virology23
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Intro to Virology Pt 228
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Herpes Zoster- Therapeutics29
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Herpes Simplex VirusesTherapeutics31
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Viral Hepatitis34
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vaccine preventable diseases pt 227
