Week 9 Flashcards
What are examples of infections caused by acellular agents?
Viruses, (viroids, virusoids, satellite RNAs, prions
What are viruses?
Virus = sub-microscopic particle (20–300 nm) that can infect the cells of a biological organism
What is the relationship between viruses and being a pathogen?
Obligate and intracellular - cannot carry out any metabolic pathway neither grow nor respond to environment cannot reproduce independently => use host cells machinery
What is a viron?
Core of nucleic acid (DNA or RNA, never both)
Protein coat = capsid
Envelope (some virions) = phospholipid membrane
What is the function of the outer surface of the virion?
Outer surface of virion (capsid or envelope) allows interaction with target cells
What are the potential genetic material of a virus?
dsDNA
ssDNA
dsRNA
ssRNA
What is the relationship between viruses and host cells?
Most viruses infect particular cell types e.g. HIV
Specific affinity of viral surface proteins or glycoproteins for complementary proteins or glycoproteins on cell surface
A few viruses are generalists – infect many cell types in
many hosts e.g. rabies
What are the stages of a ‘generic’ viral infection?
Attachment
Entry
Synthesis
Assembly
Release
What happens during attachment?
Chemical attraction of virus to host cell
How can a virus enter a cell?
Direct penetration (poliovirus), membrane fusion (measles and mumps viruses), phagocytosis (herpes virus) uncoating of capsid may be involved
What happens during the synthesis of a virus?
The manufactoring of new viruses
Different viruses (ss, ds DNA or RNA) -> different strategies
What happens during the assmebley of viruses?
DNA viruses assembled in nucleus,
RNA viruses in cytoplasm
What happens during the release of viruses?
Enveloped viruses often released by budding, naked viruses via exocytosis or lysis of cell
What are stealth viruses?
‘Stealth viruses’ – released groups of viruses within vesicles = newly identified infection route
What is the rough life cycle of an animal enveloped virus?
(a) Adsorption or docking with the host receptor protein
(b) Entry into the host cytoplasm
(c) Biosynthesis of viral components
(d) Assembly of viral components into complete viral units
(e) Budding from the host cell
What is evidence of viral disease impacting us for a long time?
Ancient Egyptians suffered polio and smallpox
Rabies, smallpox and yellow fever affected humans for centuries
Most diseases that still plague the industrialised world
Which viruses are common for human infection?
DNA - colds, chickenpox, warts
RNA - influenza
What are therapeutic approaches to viruses?
Immunisations
Treatments to alleviate symptoms
Anti-viral drugs
What is an example of an early infection of a disease?
Ramses V believed to be the first known victim of smallpox - examined pustules on his cheek
What is the overview of the history of smallpox?
Smallpox (poxviridae)
Middle ages around 80% European population contracted smallpox
18th century – European colonists introduced smallpox to native Americans; as many as 3.5 million died
First human disease to be globally eradicated in nature
What is an overview of the work by Edward Jenner?
Demonstrated immunization using mild cowpox virus (Vaccinia) to protect against smallpox (antigens are similar)
Why was eradication of smallpox possible?
Inexpensive, stable vaccine
Specificity of infection (no animal reservoirs)
Quick + obvious signs of infection (allowed quarantine)
Lack of asymptomatic cases (no carriers)
Virus spread by close contact
What is the current danger of smallpox?
Few vials in labs could be used for bioterrorism
What is the overview of smallpox?
Smallpox caused by either Variola major or Variola minor
V. major mortality rate of 3–35%
V. minor causes milder disease called alastrim and kills ~1%
Double stranded DNA linear genome ~ 200kb
How is smallpox transmitted?
Transmitted primarily through prolonged social contact or direct contact with body fluids or contaminated objects
What is the cycle of a smallpox infecting a cell?
Enters cells mainly by cell fusion, receptor unknown
Three classes of genes: early, intermediate and late (transcribed by viral RNA polymerase and associated transcription factors)
Genome replicated in cytoplasm
Virion produced after late gene expression
Transported to Golgi - two additional membranes added
Transported along microtubules and fusion with plasma membrane
What is the an overview of Polio?
Picornaviridae Enterovirus Poliovirus
Naked positive ssRNA virus (+RNA acts as mRNA)
What is the polio lifecycle for infection?
Transmitted via faecal-oral route
Infect pharynx and intestine (mucosa and lymphatic tissue)
Spread round body via viremia paralytic polio - cells of spinal cord and motor cortex of brain cytolytic - kill host cells
How can Polio be prevented?
Salk – inactivated polio vaccine (1955)
Sabin – live, attenuated, oral polio vaccine (1961)
How has the vaccine impacted Smallpox and Polio?
London - vaccine introduced 1796 deaths caused by smallpox declined
USA - Polio vaccine introduced in 1955 both paralytic cases and deaths plummated
What is an overview of the common cold?
Common cold Acute viral nasopharyngitis
Rhinovirus (as well as coronavirus, reovirus, adenoviruses)
>100 serotypes of rhinovirus cause most colds
>100,000 virions / ml nasal mucous
RNA genome
What is an overview for the common cold infecting a cell?
Entry after attachment to intercellular adhesion molecule
(ICAM)–1, ( receptor in the nasal epithelium and adenoids)
Viral infection activates several inflammatory pathways => host response is believed to be the major cause of cold symptoms Interleukin (IL)-1, IL-6, IL-8 responsible
What is an overview of Chicken Pox?
Varicella-Zoster virus HHV-3 Herpesviridae
member of large group of viruses with enveloped polyhedral
capsids and linear dsDNA similar to Simplexvirus, Varicellovirus, Lymphocryptovirus, Cytomegalovirus, Roseolovirus
How can chickenpox infect a person?
Enter host via respiratory tract
Enter host cells by attaching to receptor and fusing envelope with cytoplasmic membrane
Replicate at site of infection, spread via blood stream
Often latent infection (within sensory nerves)
Can reactivate to produce shingles
What is an overview of warts virus?
Papillomaviruses - Papillomaviridae
single molecule of dsDNA contained within a small, naked, icosahedral capsid
What happens with the infection of warts?
Papillomas – benign growths of epithelium = warts
Fingers, toes, soles of feet, body trunk, external genitalia
Transmitted via direct contact
Immune system will eventually clear infected cells, but some lesions should be dealt with
What can be caused by human papiloma virus family 16 and 18?
Known to be direct cause of cerival carinoma
How do they test for the presence of HPV and cervical cancer?
Used to only get cell sample and investigate under microscope to see if cells might develop into cancer
Now this is done after a PCR to look for HPV nucleic acids to check for infection
What is an overview of Paravoviridae?
Only human pathogens with ssDNA genome
Causes B19 disease
What is the overview of the disease B19?
Erythema infectiosum (fifth disease)
Reddening of skin (cheeks, arms, thighs, buttocks and trunk) Slap cheek - does rounds of nurseries
No treatment available (typically a mild rash illness)
What is causing an increase in emerging/reemerging viral diseases?
Infective agent’s evolution
Globalisation
Habitat modification
What is the WHO pandemic phase descriptions?
WHO pandemic phase descriptions: phase 1-6, post-peak period, possible new wave, post-pandemic period
What is an overview of HIV?
Enveloped + ssRNA viruses with reverse transcriptase
Retroviridae
Human Immunodeficiency virus (HIV)
What is the overview of HIV cell infection?
Recognition of host cell (CD4 receptor)
tRNA primes DNA synthesis = RNA / DNA hybrid
RNA degraded
Second strand of DNA synthesised
Integration into host genome
Transcription/translation, assembly of virions
Release and destruction of T helper cells
Why have HIV cases stabilised since 2000?
The use of antivirals reducing spread meaning people have a good quality life
Some people with CCR5 are more resistance -> mutanted chemokine receptor HIV cant infect cell
What is the structure of HIV?
2 copie sof RNA genome surrounded by capsid and a matirx
The spike proteins are gp41 and gp120 which binds to CD4 and co-recpetors on t-lymphocyte
What is a brief overview of influenza?
Zoonosis
1918-1919 - affected 50 million people
March 2009: new influenza virus A (H1N1) first isolated, initially disseminated in Mexico and US and then worldwide. Eight weeks later: 74 countries with ~30,000 cases and 145 deaths. June 11th 2009: “pandemic”. 2019-nCoV: Ten weeks, 118,000 cases, 4292 deaths, “pandemic” declared
What was the genesis of swine-origin influenza A/H1N1?
In pig, swine, avian and human flu mixed togther. This mega flu mixed with another swine flu then jumped into human. Creating A/H1N1
How did infleuenza enter and leave cells?
Enter through endocytosis
Leaves through budding
What is an overview of influenza spike proteins?
Hemagglutinin and neuraminidase spikes on viral surface – role in attachment
genome = 8 different -ssRNA molecules
What are the other function of Neuraminidase and hemagglutinin?
Neuraminidase (N) – hydrolyse mucous in lungs
Hemagglutinin protein (H1-16) – responsible for binding to
human receptors and trigger endocytosis
What creates new strains of influenza?
Antigenic drift and antigenic shift responsible for new strains