lecture 10 - viruses 2 Flashcards
What is smallpox?
Widely endemic in Europe/Asia
Introduced to the Americas
Exclusively human disease
Spread by person-person contact
Starts as respiratory infection
High rate of mortality 20-30%
Lead to high level of immunity
Closely related to other pox viruses which infect other animal species. DNA virus (double strand)
Describe the immunisation and eradication of smallpox
Variolation (1500 – 1700 Asia)
inoculation against smallpox using
live smallpox virus (0.5-2% fatality)
- Edward Jenner:
vaccination with cowpox (vacca = cow)
19th Century:
vaccination with Vaccinia virus
1960’s campaign to eradicate smallpox
Last case in 1977
Extinct ~1979
Smallpox eradication was possible because:
Exclusive to humans
No hidden carriers (obvious disease)
Only one serotype
Vaccination 100% successful
What are human herpesviruses?
dsDNA viruses with relatively large genomes (80 – 200 genes)
Lifelong infections
Latent cycle –
few viral proteins expressed
no virions produced
Lytic cycle –
all viral proteins expressed
virions produced to infect new cells (reactivation)
What are herpes simplex viruses?
HSV-1: Infects nerve cells. During primary infection and reactivation it manifests as ‘cold sores’. Reactivation due to “stress”.
HSV-2: genital
What is the polio virus?
Positive strand ssRNA virus
Linear genome
Related to Rhinovirus (colds)
& Foot and Mouth virus.
Small (28nm)
Genome codes 4 proteins
What is poliomyelitis?
Oral route of infection.
Infects gut, then invades blood.
Targets nerve cells (specific receptor) and destroys them.
Leads to paralysis of infected tissues.
How could vaccination against the polio virus work?
Importantly:
No asymptomatic carriers for Poliovirus in immunocompetent individuals
No non-primate reservoir in nature
Infection control and prevention could lead to worldwide eradication.
Inactivated (dead) and attenuated (live) vaccines
Inactivated (killed): treated with formaldehyde
(Salk, 1955)
Prevents entry to nerve cells, but infection of gut remains.
Attenuated: attenuated (cell culture).
Sabin 1959.
Induces immunity in the gut, prevents infection.
Discuss the advantages vs disadvantages of Inactivated vs Attenuated polio vaccines
Inactivated (killed): Advantages: Effective Can be incorporated into routine immunizations with DPT Good stability in transport and storage No risk for poliomyelitis in recipients and contacts Safe for immunodeficient individuals Disadvantages: Does not induce local (gut) immunity Booster vaccines required Administered as injection Higher community vaccination levels required
Attenuated (live): Advantages: Effective Lifelong immunity Induces immune (antibody) response similar to natural infection Indirect community immunization through spread of the attenuated virus Administration (oral) Booster vaccines not required Disadvantages: Vaccine-induced (iatrogenic) poliomyelitis Spread to contacts without consent Unsafe for immunodeficient individuals
What is influenza?
Influenza A, B, and C serotypes Negative ssRNA virus Serotype A = most serious Related to mumps and measles viruses ssRNA negative strand virus
Segmented genome = 8 fragments
Produce 10 proteins
Nucleoprotein = helical
No defined shape = polymorphic
Enveloped
Describe the envelope structure of influenza
Two important proteins:
Hemagglutinin (HA) : Attaches to host receptors
Neuraminidase (NA) : Breaks down sialic acid to allow budding
Describe antigenic variation in influenza
Antigenic drift - Minor mutations occur as a result of the low fidelity viral polymerase.
Antigenic shift - major reassortment of genome segments - Viruses infecting different species recombine (in a permissive host) leading to major genomic changes (reassortment of viral genome).
What are influenza epidemics and pandemics?
Epidemics (seasonal flu)
Associated with antigenic drifts
Cause seasonal flu outbreaks (localised)
Cycle: every 2 – 3 years
Pandemics
Associated with antigenic shifts
Worldwide outbreaks – increased severity
Cycle: every 10 – 40 years
What are influenza reservoirs?
Many flu viruses found in
Birds and pigs.
Pathogenic strain = H5N1
Can spread to other animals
Usually not transmissible from human to human.
Serious concerns for antigenic shift
or progressive antigenic drift that would result in human-to-human transmission.
What are anti-influenza drugs?
Drugs: Amantidine
Target: M2 protein on envelope.
Mode of action: Stops un-coating of virus in the cell;
Some strains of influenza resist through mutation of M2
Drugs: Oseltamivir (Tamiflu), Zanamivir (Relenza)
Target: Neuraminidase on envelope
Mode of action: Stops budding of virus
Describe flu vaccination
Killed vaccine
Comprise at least 3 strains
80-90% effective.
Need to predict future strain
Can take 6-9 months
Live cold adapted strain
Recombinant HA vaccine Vaccine targeted to: Elderly Young children Patients with respiratory conditions Individuals in high risk occupations (NHS workers)
What is HIV?
HIV is a retrovirus = RNA virus which replicates through a DNA intermediate
HIV-1 99% of infections
HIV-2 is less virulent (confined to W. Africa)
Single strand RNA virus (2 copies per virion)
Enveloped virus
The HIV genome contains 3 regions:
1. gag internal structural proteins
2. pol Reverse transcriptase + integrase
3. env envelope protein
What are the origins of HIV infection?
HIV originated from Simian Immunodeficiency Virus (SIV)
SIV infects apes (Chimpanzees and Gorillas in Africa)
Hypothesized that Zoonosis (species jump) occurred during handling of infected meat (due to a cut or bite)
Describe HIV disease pathology (AIDS)
Infection
1) Infects cells of the immune system
(T-lymphocytes and macrophages)
2) Progressively destroys immune cells, impairs their function and reduces numbers
3) Weakening of the immune system results in increased susceptibility to opportunistic infections
4) Inability to battle secondary infections leads to disease and death
Transmission occurs via bodily fluid exchange
High risk activities:
Intravenous drug use
Unprotected sex
Blood (Transfusion prior to screening)
What are the features associated with AIDS?
Definitive Diagnostics (1993):
Very Low CD4+ T-cell counts:
less than 200 / mm3 whole blood
or
less than 15% of B+T lymphocyte population
Or
AIDS-specific conditions:
Fungal infections: candidiasis, cryptococcosis, histoplasmosis,
Pneumocystis jiroveci pneumonia
Bacterial infections: Mycobacterium, cytomegalovirus (CMV) retinitis
Viral cancers: Kaposi’s sarcoma, Hodgkin’s Disease, non-Hodgkin’s lymphoma
How does AIDS affect Kaposi’s sarcoma?
Kaposi’s sarcoma-associated herpes virus
Persistent infection
KSHV infects immune cells and endothelial cells
Low prevalence in Northwestern Europe and North America
Endemic in sub-Saharan African and para-Mediterranean countries
Infection is largely asymptomatic
but introduction of HIV in US population dramatically increased incidence of what was previously a very rare disease
treated with highly active antiretroviral therapies in early 90s
remains the most common cancer among HIV-infected people
How does antiretroviral therapy work as an AIDS treatment?
Reverse transcription inhibitors
Stop the function of the viral reverse transcriptase; prevent generation of viral DNA.
First type of treatment introduced in 1987
Protease inhibitors
Stop the function of the viral protease that is required for processing of viral proteins and formation of new virions
Integrase inhibitors
Prevent integration of viral DNA in the host genome; inhibit viral integrase
Fusion inhibitors
Prevent the binding and fusion of HIV particles to target cells
What are the effects of plant viruses?
Cause a wide range of effects:
Stunted growth Zonation of petals Yellowing of leaves Infect a wide range of plants:
Wheat, corn and rice
Reduce yields by >50%
Yet highly valuable
tulips
How does plant virus infection take place?
Do not use host receptors Enter via wounds Can use vectors (e.g. insects) Pass from cell to cell by plasmodesmata e.g. tobacco mosaic virus.
