Viruses Flashcards

1
Q

What are viruses?

A

Viruses - obligate intracellular parasites

They are non-living in a traditional sense of replication, therefore they rely on the host cell for replication of their genomes and assembly of new virus particles
They are capable however, of Darwinian evolution
Most living organisms can or are infected with viruses
They are the most abundant ‘life-form’, with a viral mass equivalent to all prokaryotes
Most are bacteriophage: There are 10 ‘phage for every bacteria on earth

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2
Q

Why are viruses very diverse?

A

They are extremely diverse - over 40,000 isolated and 3,000 named

Diversity arises from:
Virus morphology - all shapes
Size - from 3 genes to >1000 genes
Infection outcome - Death, non-lethal to asymptomatic
Mode of transmission - respiratory, blood borne and faecal-oral route
Hosts - single cell, complex and multiple hosts
Disease progression - rapid and slow

Therefore it is difficult to define a virus

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3
Q

What are some defining properties of a virus?

A
  1. Their genomes are made of DNA or RNA
  2. Viruses protect their genomes with a protein coat (the repeated use of a single structural protein is common in viruses)
  3. Viruses can self-assemble from their components
  4. They must infect cells in order to multiply
  5. The viral genome contains all the information to build the particle and perform the entire virus life cycle
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4
Q

How would we be able to find a virus?

A

Viruses infect species in all three domains of life and all 6 kingdoms
They have been isolated from all environments: natural, man-made, aquatic, sedimentary and extreme
Most infect single-celled organisms in soil, sediment, and the open ocean

To find them:

  1. Look within organisms exhibiting obvious disease
  2. Or search for them where there is no apparent disease (either in environmental samples or new viruses in animals/insects)
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5
Q

How could we detect a virus we found?

A

In order to detect certain elements we can use:
ELISA - to detect host antibodies
PCR - detect viral genomes
Western blot - identify virus components
Direct visualisation - we can see the distinctive morphology

Due to individual virus species being not highly abundant, it becomes difficult to amplify all these viruses in cell culture as conditions will vary
This lead to virus identification techniques being developed that do not rely on cell culture amplification

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6
Q

What classification of viruses do we use?

A

Baltimore Classification
Types of Classification are based on advancements in RT/PCR, genome sequencing and reverse genetics

Class 1-7
dsDNA, ssDNA, dsRNA, (+)ssRNA via (-ssRNA), (-)ssRNA, (+)ssRNA via dsDNA and ss/dsDNA

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7
Q

Describe class I - double stranded DNA (dsDNA)?

A

This can be subdivided into two further groups

  1. Replication is exclusively nuclear - the replication of these viruses is relatively dependent on cellular factors
    e. g. Herpesviruses
  2. Replication occurs in the cytoplasm - the viruses have evolved the necessary transcription/replication factors of their genomes and are therefore largely independent of the cellular machinery
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8
Q

Describe herpes viruses?

A

There are two different pathologies

  1. Herpes simplex virus - (HSV-1) transmitted by mouth and causes cold sores
  2. Epstein Barr virus - (HSV-4) transmitted by saliva, responsible for infectious mononucleosis commonly known as glandular fever

The genome is 150,000 bps, which encodes for 80-90 genes

Mechanism:
Attachment to the cell surface, uncoating, entry of genome into the nucleus, replication of DNA by the viral-DdDp, transcription and export of viral mRNA, translation of viral proteins, assembly and release

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9
Q

Describe class IV - single stranded +sense RNA, (+)ssRNA?

A

This can be subdivided into two further groups

  1. Viruses with polycistronic mRNA meaning the genome RNA forms the mRNA, which is translated to form a polyprotein product (then cleaved into mature proteins)
  2. Viruses with complex transcription - two rounds of translation or sub-genomic RNAs that are necessary to produce the genomic RNA
Main properties:
The genomic virus is message sense
They replicate in the cytoplasm
e.g. Picornaviridae
These viruses are responsible for the common cold, polio and FMDV
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10
Q

Describe class V - (-)ssRNA and class VI - (+)ssRNA with DNA intermediate?

A

Class V - (-)ssRNA:
This is responsible for influenza
It has 8 segments of linear (-)sense ssRNA, not like mRNA

Class VI - (+)ssRNA with DNA intermediate:
These can be lentiviruses: HIV

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11
Q

What unique elements make viruses diverse?

A

Double/single stranded, DNA/RNA
Linear/Circular
Segmented/Non-segmented
+ or - sense

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12
Q

What are capsid proteins?

A

Usually highly positively charged (basic) proteins - rich in arginine and lysine Role - to package nucleic acid
They have nucleic acid binding proteins (specific and nonspecific interactions)
They self assemble

Non-enveloped viruses - poliovirus

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13
Q

What are icosahedral viruses?

A

They are genome protection vehicles
The helical arrangement allowed symmetry and strength
However, the viral nucleic acid alone can be infectious

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14
Q

How are the genomes protected in icosahedral viruses?

A

They have a matrix, lipid bilayer and an envelop glycoprotein surrounding the capsid and the genome

Enveloped viruses - HIV, herpes simplex

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15
Q

What are triangulation numbers associated with icosahedral viruses?

A

Many viruses are based on icosahedral symmetry - 20 sides
Each side can be split into 3 - giving multiple copies of one or more proteins
Therefore 60 subunits
T = 1 (one side that is split into 3)
But trying to subdivide any further can break symmetry

Not all proteins are in equivalent positions: pentamers and hexamers
You need a five and six-fold particle axes to make it work

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16
Q

Why do we need viruses to exploit genetic economy?

A

They need to produce some of their own components
Picornaviral capsid proteins - produce one long polyprotein, they produce their own proteases to cleave into proteins
MS2 - has more pores and is quite sparse
A genome under pressure can mean fast release

17
Q

Describe the influenza virus?

A

Influenza viruses - Orthomyxoviruses
Genome structure - segmented
8 segments encode for different proteins
It doesn’t always package all 8 - 7+1 arrangement
It has packaging signals

18
Q

Describe ebola virus?

A

Ebola:
This has a negative sense genome
900 nm - huge, and can almost be seen under a light microscope

19
Q

What is the history of some pandemics?

A

Spanish Flu pandemic of 1918 - around 50 million died

Swine Flu 2009 - the first influenza pandemic of the 21st century
Both are subtype H1N1

West Nile Virus - infects birds but can be transmitted to humans through mosquitos
This can produce asymptomatic infection, mild febrile syndrome and a neuroinvasive disease - West Nile meningitis or encephalitis

Foot and mouth disease - highly infectious, Great Britain 2001 - world’s worst epidemic
Picornavirus, causes blisters in the mouth and feet of bovids and other cloven-hoofed animals
10 million sheep/cattle were killed

20
Q

Why do infectious disease emerge/re-emerge?

A

Microbial adaption e.g. genetic drift and genetic shift in Influenza A
Climate and weather - e.g. mosquitos move further from the tropics as the climate warms
Change in human demographics and trade - e.g. humans travelling enabled SARS to rapidly move around the globe
Economic development - antibiotic resistance
Changing human susceptibility - e.g. mass immunocompromisation with HIV/AIDS
Breakdown of public health
Poverty and social inequality
War and famine
Bioterrorism - e.g. 2001 Anthrax attacks
Dam and irrigation system construction - e.g. malaria and other mosquito borne diseases

21
Q

What are some routes of viral transmission?

A
Inhalation (respiratory tract)
Intravenous (blood)
Abrasion (skin)
Ingestion (GI tract)
Sexual contact (genital tract)
Mother to baby
22
Q

Describe the respiratory tract route?

A

It is protected by mucus, ciliated cells, alveolar sacs lined with macrophages and antibodies
Viruses enter in the form of aerosolised droplets or saliva - usually enveloped viruses
They infect the host by attaching to a cellular receptor located on ciliated epithelial cells of the respiratory tract

Examples: Rhinovirus, Coronavirus (SARS), Influenza A and B, Respiratory syncytial virus, Adenovirus and Coxsackie A21, B4

23
Q

Describe the gastrointestinal tract route?

A

Aka - oral-faecal route
Virus shed in faeces gotten into someone’s mouth and ingested into the stomach
A virus would have to be acid stable, resistant to salts and proteases - pH 2 in the GI tract
The constant movement of liquefied food through intestinal tract allows virus time to attach and infect intestinal epithelial cells

24
Q

Give some examples of gastrointestinal tract viruses?

A

Examples: Rotavirus, Sapovirus, Polio, Norovirus and Enteric Adeno

Norovirus - Transmitted by faecally contaminated food or water, by person-to person contact, and via aerosolization of the virus (via vomiting)
Outbreaks occur in closed spaces: hospitals, prisons and cruise ships

Polio - when the virus enters the central nervous system and replicates in motor neurons it causes selective destruction leading to muscle spasms and paralysis

25
Q

Describe the skin route?

A

This is a natural barrier microorganisms
Outside - hostile environment (dryness, acidity) as it comprises of dead cells (viruses need living cells to replicate)
Viruses can enter through bites, needlesticks and abrasions

During transfusions of blood before 1995, no blood was screened - HIV and Hepatitis B/C were prevalent
Hep C leads to scarring of the liver and in some cases liver failure

26
Q

Describe the genital tract route?

A

Sexual activity may produce tears or abrasion in the vaginal epithelium, trauma to the urethra, anus or throat
Sexually transmitted viruses - HIV, HPV, HSV-2 (genital herpes)

27
Q

How can viral infections be prevented/treated?

A
Vaccination
Anti-viral agents
Slaughter
Isolation
Education
28
Q

How do vaccines work?

A

A vaccine must stimulate as many of the body’s defence mechanisms as possible
Herd immunity - when a sufficiently high proportion of a population has been vaccinated that the virus struggles to jump host
Vaccination has eradicated smallpox

29
Q

How do anti-viral agents work?

A

Many viruses have evolved their own specific enzymes to replicate virus nucleic acids preferentially at the expense of cellular molecules
There is often sufficient specificity in virus polymerases to provide a target for an antiviral agent
The majority of these drugs function as polymerase substrates analogues
However, typical serum half life is 1-4 hours

30
Q

What is a recent case study?

A

Coronaviruses - one of common cold viruses
2002-03 SARS - Serve acute respiratory syndrome
An outbreak in Hong Kong nearly became a world wide pandemic
It infected 37 countries
8,422 cases and 916 deaths worldwide (11.9% fatality)
The natural host is the bat

Now - MERS-CoV
In 2012 it was discovered
238, with 92 deaths
Not highly contagious

NOW NOW - COVID-19