Viruses Flashcards
1
Q
what are viruses
A
viruses are obligate intracellular parasites
2
Q
describe viruses and what they depend on
A
- They parasitise all biomolecular aspects of life.
- They depend on the host cell for all raw materials and energy (e.g. nucleotides)
- Replication can only occur within a host cell
3
Q
in what forms do viruses exist
A
- An extracellular virion containing DNA/RNA (genome)
- as nucleic acid inside the host cell.
4
Q
what are the two main structures of viruses and how do they differ
A
-
Enveloped virus:
- First is a capsid containing viral nuclei acid.
- virus buds out of the infected cell it and takes some of the plasma membrane, embedded with viral glycoproteins, with it.
- plasma membrane generates the envelope of the virus.
- The glycoproteins embedded on the membrane gives the virus its host cell specificity
- cus glycoproteins interact with receptors on surface of cell.
- Eg: Pox virus, Herpes virus
- Basically the cell plasma membrane that it takes forms the envelope around the capsid
- cus glycoproteins interact with receptors on surface of cell.
-
Non-enveloped virus:
- These viruses don’t contain plasma membrane studded with glycoproteins.
- just have a capsid containing viral proteins on the outside which then interact with cell surface.
- The Capsid contains nucleic acid.
- Eg: adenovirus or rotavirus
5
Q
what gives viruses their host cell specificity
A
The glycoproteins embedded on the membrane gives the virus its host cell specificity
6
Q
genome size in RNA vs DNA viruses
A
- RNA → genome smaller
- DNA → enormous range in size
7
Q
what was the guy who did the classification
A
Baltimore
8
Q
Outline the Baltimore classification of viruses
A
- The system is based on how viruses generate mRNA.
- There are 7 classes
- classified according to type of nucleic acid the virus has.
- How they convert nucleic acids → mrna → protein
- Key:
- ds: double stranded
- ss: single stranded
- +: positive sense
- : negative sense
- e.g HIV: Positive sense ss RNA that needs to be reverse transcribed
- e.g. HEP B: DNA virus that has some RNA – needs to be reverse transcribed.
- : negative sense
- DNA viruses are usually always the largest viruses
9
Q
How does dsDNA virus work
A
-
dsDNA virus:
- Use DNA polymerase (cellular or viral) to replicate their genome.
- Then use cellular RNA polymerase to make mRNA.
10
Q
How does reverse RNA (HIV) work
A
- reverse RNA (HIV):
- Carries 2 ss +ve sense RNA molecules as its genetic material.
- This is reverse transcribed to dsDNA, using enzyme reverse transcriptase, which can then be integrated into host cell genome.
- The viral cDNA is transported into the host cell nucleus, where it integrates into the host cell DNA. Integration is catalyzed by the viral enzyme integrase.
- The integrated provirus is transcribed by the host cell RNA polymerase II, producing viral RNA transcripts.
11
Q
+ve sense vs -ve sense RNA (dont relly need to know this but it confused me)
A
- example of each:
- -ve ssRNA virus: influenza
- +ve ssRNA virus: Hep C
12
Q
Outline the lifecycle of a virus
A
- Adsorption on to cell surface.
- Entry into cell:
- Proteins on capsid/envelope interact with receptors on cell surface.
- allows for direct fusion of cell surface with virus plasma membrane or receptor mediated endocytosis.
- Capsid transported to nucleus & nucleic acid released into nucleus (or nucleic acid released in cytoplasm)
- Transcription
- Translation
- Replication
- Capsid assembly
- Glycosylation
- Glycoprotein exported to cell surface
- Endocytosis of glycoprotein containing plasma membrane
- Envelopment of virus
- Virus release
13
Q
Why do we need to know about virus replication, How will this aid clinically
A
- so we can design drugs against viruses
- These work by inhibiting each stage in their replication:
- DNA polymerase inhibitors
- Reverse transcriptase inhibitors: nucleoside or non-nucleoside inhibitors
- Viral protease inhibitors
- Viral neuraminidase inhibitors
- Inosine monophosphate dehydrogenase inhibitors
14
Q
List some clinically significant viruses
A
- Influenza virus - causes just Acute infection.
- Hepatitis B and Hepatitis C viruses: cause both Acute and Chronic infection.
- Human immunodeficiency virus: causes just Chronic infection.
- Herpesviruses: causes a Latent infection.
15
Q
Outline the general structure and material of an influenza particle
A
-
Structure: Enveloped virus - envelope studded with viral glycoproteins
-
Genetic material: Segmented, negative sense, single stranded RNA
- There are 8 segments in total
- Each RNA segment encodes for separate proteins.
- The most important segments:
- Segment 4 HA: encodes for Haemagglutinin (blue)
- Segment 6 NA: encodes for Neuraminidase (orange)
- Segment 7 M2: Ion Channel (green)
-
Genetic material: Segmented, negative sense, single stranded RNA
16
Q
What are the 3 types of influenza viruses which can effect humans, which type is the most important
A
- A Causes pandemics - infects humans, horses, pigs, birds
- B Causes seasonal epidemics - infects only humans
- C Mild respiratory illness - infects humans and pigs
- A is the most important as it causes pandemics
17
Q
Influenza virus can be divided into subtypes based upon which 2 viral proteins
A
- Haemagglutinin (H1 – H18) (18 different types)
- Neuraminidase (N1 – N11) (11 different types)
- E.g. H5N1 – made up of H5 and N1 proteins.
18
Q
How else can influenza be classified
A
The virus can also be classified as avian, swine or other types of animal influenza.
19
Q
which cells do influenza target
A
airway epithelium
20
Q
How does the influenza virus particle enter target cells
A
- The influenza virus’ target cell – air way epithelium.
- Influenza Haemagglutinin (HA) mediates entry into target cell
- HA protein needs to interact with a sialic acid receptor on surface of the epithelial cell for virus to enter cell
- In man this is Alpha 2,6 Sialic acid.
- Alpha 2,3 Sialic acid is avian Sialic acid receptor.
21
Q
How do neutralising antibodies inhibit the interaction between HA and sialic acid
A
- HA interacts with Alpha 2,6 Sialic acid on surface of the airway epithelium.
- induces receptor mediated endocytosis of the virus → the cell.
- stimulates neutralising antibodies to be produced.
- antibodies binds to HA
- blocks interaction and this blocks virus entry into target cell.
22
Q
Why do we repeatedly get infected with the influenza virus (Influenza virus haemagglutinin (HA))
A
- because it is an RNA virus
- RNA is alot mote unstable than DNA so can accumulate mutations very quickly
- This is because of ANTIGENIC VARIATION (2 types)
- Antigenic Drift
- Antigenic Shift
23
Q
What is an antigenic drift
A
- = Small changes in the genes of influenza viruses that happen continually over time as the virus replicates.
- mutations will accumulate over time.
- Eventually the virus generates proteins that are no longer recognised by the immune system.
24
Q
How does an antigenic drift present itself in HA
A
- Via specific interaction between HA and Sialic acid receptor (SA).
1. neutralising antibodies block this interaction.
2. overtime all of the RNA segments will accumulate point mutations.
3. HA may get mutations in region where it interacts with SA.
4. mutations accumulate overtime so you get several mutations in that region.
5. mutations alter epitopes in HA so that neutralising antibodies dont recognise that part of HA-
∴ cant bind to it
- interaction of HA with SA can happen again, and so the virus can enter cell again.
-
∴ cant bind to it
- Antigenic drift mainly causes epidemics
25
Q
Why are mutations leading to antigenic drifts more likely in viruses such as influenza
A
- RNA viruses (such as influenzas) must replicate their genomes using RNA polymerase.
- RNA polymerase lacks the proofreading ability of DNA polymerase - so if a mutation occurs it is not exercised.
- you get accumulation of point mutations every time the RNA genome is replicated
- RNA viruses have a greater mutation rate than DNA viruses.
- ∴ rapidly alter antigenic epitopes targeted by the immune system
26
Q
What can antigenic shifts in Influenza A viruses result in, Why is this clinically relevant
A
- An abrupt, major change in the influenza A viruses
- resulting in completely new Haemagglutinin and/or neuraminidase proteins.
- results in a new influenza A subtype.
- People do not have immunity to the new (e.g. novel) virus as we have never seen it before
- most likely to causes a pandemic.
27
Q
Why is Antigenic shift unique to Influenza A
A
- because influenza A has a segmented genome
- if you get infection of one cell with 2 different viruses, there can be the swap of RNA segments between the different viral strains.
- results in the creation of a new virus with new HG/NM proteins.
- So you have no cross-protective immunity to the virus expressing a novel hemagglutinin (this HA never seen by humans)
28
Q
What significant pandemics have arose as a result of antigenic shifts
A
- 1957 Asian Influenza:
- Emergence of H2N2.
- The H2N2 avian virus and H1N1 human virus swapped fragments:
- 2 of avian fragments were substituted for 3 human fragments.
- This creates a new HG and new NM. T
- 1968 Hong Kong Influenza:
- H3 avian virus fragments swapped with H2N2 fragments leading to brand new HA and polymerase.
29
Q
How can antigenic shifts result in viruses transferring between species, is it possible
A
- humans:
- SA receptors present at the top of the respiratory tract are mostly alpha 2,6.
- Alpha 2-3 SA receptors are only found at the very bottom of lungs.
- birds:
- the alpha 2,3 MAA-I is expressed high up on the respiratory tract and also deep as well.
- also found deep in the alimentary canal.
- So very unlikely that there will be direct transmission of influenzas from birds → humans.
- Pigs
- mixing pot for the generation of new influenza strains.
- express high levels of alpha 2-6 and alpha 2-3 in their upper respiratory tract.
- So, it is thought bird avian influenzas human influenza will coinfect pig.
- then get antigenic shift creating an new generation of virus which can then infect man leading to pandemic.
30
Q
Outline the structure of the Hepatitis B virus
A
- Small enveloped dsDNA virus studded with Hepatitis B surface antigens.
- small, medium and large surface antigens
31
Q
When is the E antigen expressed
A
only expressed when the virus is in replication
32
Q
How many genotypes are there and how big is the virus
A
- 8 viral genotypes
- It is a small virus – contains 2.3kb of DNA.
33
Q
What can you see in an electrograph of Hepatitis B
A
- Intact viral particles called Dane particles
- Round particles with electron dense centre where nuclei acid sits
- Spheres + Tubules are made up of purely hep B surface antigens.
34
Q
How infectious is hepatitis B and how long does it last outside the bod
A
- extremely infectious (50 – 100 x more infectious than HIV).
- remains infectious outside the body for up to 7 days
- so important to clean medical equipment used on people with HEP B
35
Q
How is hepatitis B transmitted (6)
A
- Perinatal transmission = mother to child at birth
- Parenteral transmission = blood, blood products
- Needle stick injury, tattooing, piercing
- Sexual
- Infected body fluids → saliva, menstrual, vaginal, seminal fluids
- Medical/surgical/dental instruments
36
Q
What groups are at higher risk of Hepatitis B infection
A
- Health care workers
- Men who have sex with men/multiple sex partners/sex workers
- Blood transfusion recipients(blood screened very highly so unlikely)
- I.V. drug users
- Infants of HBV carrier mothers
- Recipients of solid organ transplants
37
Q
What is the incubation period of hep B
A
30 to 180 days, mean 75 days → can infect ppl without knowing you have the virus
38
Q
How do people with acute Hep B infection present
A
- Acute infection
- Infection is usually mild, particularly in children.
- 30 – 50% adults present with jaundice and hepatitis.
- Severity
- Ranges from Asymptomatic subclinical ⇒ fulminant fatal.
- Acute infection either disappears or can develop into a chronic infection
39
Q
What is the prevalence of chronic Hep B infection
A
- Infants are far more likely to get chronic infection than adult.
-
Infants:
- 80 – 90% Infected during first year of life will get a chronic infection
- 30 – 50% of children infected before age of 6 will get chronic infection
-
Adults:
- <5% of otherwise healthy adults will develop chronic infection
- 20 – 30% who are chronically infected will develop cirrhosis and/or liver cancer
40
Q
How is a acute hepatitis B virus infection tested for in the lab
A
- test them for antibodies to diagnose the infection.
- When a person gets infected you first see a rise in Hep B E antigen (HBeAg)
- indicative of virus replication (purple line
- There’s a lag phase where you start to develop antibodies against the virus.
- develop IGM antibodies (orange) and IGG antibodies.
- Green line = total antibodies (IGM + IGG antibodies).
- you will develop antibodies (HBsAg) against the Hep B surface antigens (blue line)
- HBsAg = surface antigen
- These will last for a lifetime.
- The Hep B surface antigen is what you are vaccinated against.
- Summary: Effective host response to Hep B
- Loss of HBeAg
- Appearance of HBe antibodies
- This should result in clearance of Hep B virus DNA and HBsAg
41
Q
How is chronic hepatitis B virus infection tested for in the lab
A
- You will get viral replication (purple line) but this viral replication will stay on and not decrease.
- So you get months to years of expression of HBeAg (antigen) - diagnostic of chronic infection.
- You will get antibodies to total Hep B core and also get IGM antibodies
- Chronic infection:
- Continued viral replication
- Detect Viral DNA, HBsAg (surface antigen and HBeAg in serum)
- This will result in Elevated serum alanine and aspartate aminotransferase (ALT/AST) levels – indicates liver damage.
42
Q
Outline the stature of a hepatitis C viruS
A
- Enveloped ssRNA virus
- Envelope is studded in glycoproteins GP1 and GP2.
- Small virus
43
Q
How is the hepatitis C virus seen on the electron microgrph
A
- always see the virus attached to lipids or lots of lipid droplets.
- because the Hep C virus embeds or attaches itself to lipids – specifically low-density lipoproteins.
- lipids interact with cell surface to bring virus in close proximity to cell to enable viral entry into cell.
- I.e. viral entry into host cell is not initiated by envelope glycoproteins but initiated by low density lipoproteins.
44
Q
How does hepatitis C transmission occur
A
- Purely Bloodborne
- Injecting drug use/sharing injection equipment
- Reuse or inadequate sterilization of medical/surgical/dental equipment (esp. syringes/needles)
- Transfusion of unscreened blood and blood products
- Sexual practices that lead to exposure to blood
- Perinatal transmission is less common
45
Q
What is the Incubation period of Hep C
A
- 2 weeks to 6 months (less than Hep B)
46
Q
What is the acute infection and chronic Hep C prevalence
A
- Acute infection
- 80% asymptomatic
- 20%: fever, fatigue, decreased appetite, nausea, vomiting, abdo pain, dark urine, joint pain, jaundice.
- Severity
- Asymptomatic subclinical ⇒ fulminant fatal.
- Chronic infection
- Infants: 50 – 60% of all infants who get infected will get chronic
-
Adults: 50 – 90%
- 20 – 30% who are chronically infected will develop cirrhosis and/or liver cancer
47
Q
How does HIV link with the hepatitis C virus
A
- Approx 2.3 million people (6.2%) of the estimated 3.7 million living with HIV have serological evidence of past or present HCV infection.
- Chronic liver disease major cause of morbidity and mortality in persons living with HIV.
48
Q
How is hepatitis C virus detected for in a lab and subsequently diagnosed
A
- Antibody testing – many people are asymptomatic
- tests historical infection
- Viral nucleic acid testing done if antibody test is positive
- tests for Current infection
- Check for cirrhosis
- Graph- Once infected by HEP C virus RNA levels will rise first – this indicates of viral replication.
- Then you get lag phase before you get antibodies that show up.
- ALT tests liver function – levels fluctuate
49
Q
Explain why Hep C has so many genotypes
A
- It’s an RNA virus so it does not have proof reading capability.
- So it can undergo genetic mutation and accumulation overtime.
- Accumulation of mutation in Hep C has resulted in different genotypes 1-6 and mixed (infected by many genotypes).
- In places such as Europe and NA the predominant strain is strain1
50
Q
How is chronic Hep C treated
A
antivirals (95% of cases):
- The treatment you use in children is dependent on the genotype of Hep C that they have.
- This is not the case in adults
- No vaccine
51
Q
Name the 8 different human herpes viruses
A
- Herpes simplex virus 1 (HSV-1) → cold sores
- Herpes simplex virus 2 (HSV-2) → STD
- Human cytomegalovirus (HCMV)
- Varicella-zoster virus (VZV) → chicken pox
- Epstein Barr virus (EBV) → glandular fever (kissing one)
- Human herpesvirus 6A/6B (HHV-6A/6B)
- Human herpesvirus 7 (HHV-7)
- Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8)
- 1 & 2 cause oral and genital herpes.
- 4 – causes chicken pox
- 5 – glandular fever
- 8 – causes Kaposi sarcom
