Pathogens (Jeremy Lecture 1) Flashcards
Name some common features of all viruses
1) Package their genome inside particles that allow for transmission
2) Viral genome contains info necessary to direct viral replication in a permissive host
3) Must make mRNA that can be translated by the host ribosomes
4) Survival depends on a balance of host-pathogen interactions
- Replicate too fast and/or cause too serious disease, kills host, limits spread
- Replicate too slow or too passive, cleared by host immune system
What are the 7 classes of viral genomes?
- dsDNA
- gapped dsDNA
- ssDNA
- dsRNA
- ss (+) RNA
- ss (-) RNA
- ss (+) RNA with DNA intermediate
n.b. all viruses must be able to produce mRNA, so many viruses need mechanisms to do this e.g reverse transcriptase for reverse transcription
Where do RNA virus and DNA viruses tend to replicate? Give an example of an exception
Most RNA viruses - cytoplasm
Most DNA viruses - Nucleus
DNA Pox viruses replicate in cytoplasm
RNA influenza viruses replicate in the nucleus
What are the common set of assembly reactions that occur in all virions?
1) Formation of structural units of the protein shell (capsid) from one or several viral proteins
2) Assembly of the capsid
3) Packaging of the nucleic acid genome and other essential virion components
4) Release from host cells
The steps are common to all viruses
In some viruses:
- the capsid also gains an envelope
- Virion maturation after release
What different durations can a viral infection have?
Can be short-lived acute infections to infections that last for the life of the host
What is viral pathogenesis dependant upon?
The interaction between the virus and the host responses
What factors effect viral pathogenesis?
- Viral route of host entry
- Initial host reponse (innate)
- Site and effect of primary viral replication
- Viral virulence factors
- Extend of viral spread within host
- Host clearance (adaptive)
- Transmission to next host
What are the main viral sites of entry?
Mainly mucosal surfaces
Sometimes skin, but harder to penetrate and thrive
Epidermis very effective barrier
What are the effects of viral virulence factors?
- Enhance virus replication
- Minimise host replication
- Modify host defenses
- Facilitate viral spread
- Killing of host cells
What is the term for when a virus spreads beyond the site of infection?
Disseminated
What is the term in the virus spread affects many organs?
Systemic
How can a disease be linked with a particular pathogen?
Koch’s postulates (for more info see questions on Ians slides)
What are the 3 types of acute viral infection and give a virus that causes each
1) Viral clearance and resolution (able to repair damage caused)
- Influenza virus
2) Viral clearance and incomplete resolution
- Poliovirus
3) Incomplete clearance and lethality
- Ebola virus
What are the 3 types of chronic viral infection and give a virus that causes each
1) Progressive
- HIV
2) Latent/re-occuring
- Herpes virus
3) Transforming/malignant
- Papilomavirus
What is essential for acute viral infection clearance?
Induction of the adaptive immune system
Give some examples of viruses that cause acute infection?
Influenza Poliovirus Measles Rotavirus West Nile virus
What are the characteristics of the influenza virus?
- Orthomyxovirus
- Segmented-sense ssRNA genome
- Enveloped
- Types A, B and C
- A and B cause most human disease
- Antigenic shift and drift
- Virulence factors differ by strain
- Mild, self-resolving upper respiratory track illness
What are the symptoms and characteristics of influenza disease?
- 1-5 day incubation period
- Abrupt onset of headache, chills, cough, fever, malaise
- Fever peaks day 1, declines by day 3, gone by day 6
- Respiratory symptoms increase as fever declines
- Cough and malaise can last for 2 weeks
- Caused primarily by viral cytolysis and immunopathology
What can be the complications of influenza disease?
- Pneumonia
- Secondary bacterial pneumonia
- Neural syndromes e.g. meningitis
What are the characteristics of polio virus?
- Picornavirus
- +sense, ssRNA genome
- small and unenveloped
- 3 serotypes
- can cause mild disease or poliomyelitis (paralysis)
- 2 available vaccines
Describe normal polio replication vs severe polio replication and spread
- Normally, polio replicated on mucosal surfaces causing either no symptoms or mild fever
- Sometimes, if virus breaches mucosa, it enters the lymph node, then the blood (viremia), then to the spinal cord where is affects motor neurons resulting in poliomyelitis
What are the symptoms and characteristics of poliovirus disease?
- Fecal-oral transmission
- 3-35 day incubation period
- Acute infections cleared by immune system
- Typically causes asymptomtic infection or mild fever
What are the 2 complications of poliovirus?
1) Poliomyelitis (paralysis)
- spread and replication in motor neurons and encephalitis if spreads to spinal cord
2) Post-polio syndrome (muscle weakness)
- 30-40 years after resolution due to lingering damage to motor neurons
What are the chaaracteristics of Ebola virus?
- Filovirus
- -sense, ssRNA genome
- Filamentous and enveloped
- 5 species and 2 related filoviruses (marburg)
- Sporadic outbreaks in Africa
- Severe haemorrhagic disease
What animals are the likely disease reservoir for Ebola virus?
Fruit bats and infected monkeys
What contact is required for Ebola transmission?
Direct fluid contact
What is the incubation period of the Ebola disease and describe the disease progression
- 2-20 day incubation period
- 1-10 day prodrome phase with severe flu-like symptoms
- 7-15 days - haemorrhagic symptoms that rapidly lead to multiple organ failure and death
What are the 2 Ebola strains and what is the case fatality of each?
1) Zaire ebolavirus
90% case fatality
2) Reston ebolavirus
0% case fatality
What causes the disease in Ebola virus infection?
Dissemination of the virus followed by widespread cell death and a fatal inflammatory response (‘cytokine storm’)
When do chronic infections occur?
When the primary (acute) infection is not cleared by the adaptive immune response
What are the characteristics of the HIV virus?
- Retrovirus
- +sense, ssRNA genome
- Enveloped
- 2 strains: HIV-1 and HIV-2, but HIV-1 most associated wit disease
What is the disease associated with HIV infection?
Acquired Immune Deficiency Syndrome (AIDS)
How is HIV transmitted?
Virus in the blood: - Transfusions - Needle sharing - Tattoos Virus in semen and vaginal secretions: - Anal and vagina intercourse Perinatal transmission: - Interuterine transmission - Breast milk
What are the mechanisms of AIDS?
- HIV infects mainly CD4+ T cells and macrophages
- Integrates its genome into host chromosomes
- Lyses CD4+ T cells, persistently infects macrophages
- Killing of CD4+ T cells causes immunosupression
- Many immune cells are affected as CD4+ cells are helper cells and therefore regulate other immune functions
What are the characteristics of herpes simplex virus?
- Herpesvirus
- Linear dsDNA genome
- Enveloped
- 2 types of HSV and 8 related herpesviruses
- Life long latent infection
What occurs during acute phase HSV infection and what is caused?
Virus infects epithelial cells of oral mucosa and can cause mucosal lesions
How does the infection becomes chronic?
- Virus breaches the mucosa and spreads to the sensory neurons
- Latency (non-replicative state) is established by silencing of the genome and is maintained by the LAT transcript
- Triggering events can occur to reactivate virus, spread back to oral epithelium and reestablishement of acute infections
What are the characteristics of the Human Papillomavirus?
- Papillomavirus
- Circular dsDNA genome
- Non-enveloped
- Over 120 types
What diseases are caused by HPV?
- Most types cause beinign outgrowth into warts
- 2 types cause cervical cancer
- Main cause of cervical cancer
How is HPV transmitted?
- Sexual contact
What is the HPV disease mechanism?
- Infect either epithelial cells of skin or mucous membranes
- Infects basal layer of epithelium but only replicated in terminally differentiated epithelial cells
- Causes increased cell proliferation via targeting of p53 and Rb cell cycle controls
