5 Patterns of Viral Infection Flashcards
Q: List 8 methods by which viruses transmit themselves?
A: respiratory (exhaled/ left behind on surfaces)
faecal-oral (dirty surfaces)
contact (lesions/ saliva/ fomite- remain on surfaces)
zoonoses (from animals/insects)
blood (transfusions/ injections)
sexual contact
maternal-neonatal (could be placenta)
germline (eg retroviruses)
Q: Transmission terminology. Define iatrogenic transmission.
A: due to medical conditions (eg contaminated needles)
Q: Transmission terminology. Define nosocomial transmission.
A: acquired in hospital
Q: Transmission terminology. Define vertical transmission.
A: from parent to offspring
Q: Transmission terminology. Define horizontal transmission.
A: all other forms- transmitted among individuals of the same generation
Q: Transmission terminology. Define germline transmission.
A: part of the host genome (e.g. integrated retrovirus)
Q: Name 3 physical barriers to virus entry.
A: skin
mucosal surfaces (respiratory, enteric, genital tract)
conjuctiva (the mucous membrane that covers the front of the eye and lines the inside of the eyelids)
Q: What are viruses that are spread by insects called?
A: arboviruses
Q: Name the 5 possible stages for viral dissemination from the site of entry. What are the 2 broad options following entry?
A: once virus has entered the body -> may stay and replicate at original site or disseminate from that site
Local Infection
Primary Viraemia
Amplification
Secondary Viraemia
Target Organ
Q: Give an example of a local infection? (in terms of viral dissemination). Where does it replicate? entry? exit?
A: rhinovirus- common cold
replicates in nose and exits
apical entry and apical release
Q: Describe primary varaemia. (in terms of viral dissemination). Process? exit?
A: enter local place -> disseminate through polarised epithelial -> into blood below (-> could make way to organ and amplified)
some viruses cause it
dissemination and basal release (side close to blood)
Q: What does viraemia mean? haematogenous?
A: viruses in blood
originating in or carried by the blood
Q: What can amplification also be called? (in terms of viral dissemination)
A: systemic (spread through body)
Q: Why do viral rashes form? How?
A: due to systemic viral infection
when virus leaves body, often leaves a rash behind (travels via blood-> exits and enters skin)
cells of skin are destroyed by virus replication
Q: What can a measles infection cause in terms of viral rashes?
A: koplik spots in mouth
Q: What do you get before skin rashes in measle and chicken pox?
A: lesions on mucous membranes of soft respiratory tract tissues
Q: When do you tend to get symptoms for (varicella zoster virus) chicken pox?
A: after secondary viraemia
Q: Describe the dissemination of the varicella zoster virus (VZV chicken pox). (6)
A: 1. virus is acquired through upper respiratory tract/eye
- replication in primary lymph nodes
- travels towards blood
- goes to liver, spleen, etc
- secondary viraemia
- reach neurones -> affect sensory neurones (where it remains latent)
Q: Which 2 cells can the varicella zoster virus affect?
A: skin cell
PBMC peripheral blood mononuclear cell
Q: What can the varicella zoster virus cause in most childhood cases? In adulthood what happens? result?
A: mild self limiting illness
(herpes zoster/shingles) occurs in adulthood when cellular immunity is impaired- virus is reactivated in the sensory neurones and causes painful rash at the nerve endings
Q: Define tropism. What is it defined by? (3)
A: The predilection of viruses to infect certain tissues and not others
- Susceptibility - receptor interactions (eg HIV and CD4 ‘receptor’)
- Permissivity - ability to use the host cell to complete replication (inside the cell- machinery)
- Accessibility - ability of the virus to reach the tissue (physical issue)
Q: What determines the tropism of HIV? Summarise.
A: receptor use
CD4 is used by all HIV but in terms of co receptor, either use CCR5 or CXCR4
Q: What’s the viral attachment protein of HIV?
A: gp120
Q: What confers HIV resistance? means?
A: delta 32 mutation in CCR5
if exposed to HIV, won’t get infected
Q: Describe the tropism switch during HIV replication. How can we use this to aid treatment methods?
A: 2 different strains
macrophages-tropic strain of HIV-1: attaches to CD4 and beta-chemokine receptor (CCr5) which is common in macrophages
T cell-tropic strain of HIV-1: attaches to alpha-chemokine receptor (CXCr4) which is common in T cells
transmission of HIV is very often through macrophages: transmitted strains tend to have gp120 that matches to CCr5 but once transmitted, being highly mutable, -> lots of mutant strains derive from it -> some of those can bind to CxCr4 (these ones drive loss of CD4 cells)
if we delay evolution of switch -> slow decay of immune system
Q: What are the receptors used by the measles virus? (4) Where are they in the body?
A: to enter: CD155 or SLAM (SLAM is on immune cells)
to exit: Nectin 4 (airway epithelia)
CD55 used by vaccine strain Edmonson
Q: Describe the measles virus receptor use and the timeline of events from getting infected to the virus leaving?
A: airborne droplets from someone already infected -> breathed into respiratory tract and measles virus will sit in air space
dendritic cells express SLAM on surface and become infected by measles virus (dedritic cells appear occasionally between epithelia cells)
dendritic cells go back -> enter blood -> move to lymph -> go to other sites where measles virus will replicate rapidly -> spread in body
few days later
go back to blood -> go to basal layer of epithelium -> interact with nectin 4 -> replicates and divides in epithelia cells
exits cells through apical surface-> breathed out
Q: Describe influenza virus morphology. (3)
A: outside on surface: NA (neuraminidase) and HA (haemagglutinin spike protein)
inside: RNA segments
spherical
Q: How is the influenza virus’s tropism defined by receptor use? (2)
A: it’s not- influenza virus has a requirement not to do with receptor binding
the receptor used is present in all cells in body- not specific
Q: What does influenza’s HA (haemagglutinin spike protein) bind to? where? How does influenza enter? Why and how does it only affect certain cells?
A: -HA helps influenza latch onto the surface of cells
- It does this by HA binding sialic acid
- SIALIC ACID IS UBIQUITOUS - it is everywhere
=>In theory, influenza can enter any cell of your body
-Influenza only tends to affect the respiratory route - partly due to accessibility
- Once bound onto sialic acid, it enters the cell via the endosome
- Low endosomal pH allows a massive conformational change - this is essential for the virus to fuse with the endosome membrane and uncoat
- Fusion with the membrane and uncoating can only happen if the protein of the virus has been snipped in two at a particular point
This requirement of cutting the protein into two pieces is what determines the tropism of the virus
It is only in the fluid that lines our lungs that the right proteases are present.
Viruses mill around until they come into contact with the appropriate proteases which can chop the HA in two and activate the virus.
Q: How is influenza tropism extended?
A: mutation at HA cleavage site
Q: What is pathogenicity?
A: the ability of a virus to cause disease
Q: What is virulence?
A: describes the capacity of a virus to cause disease (how well does it replicate)
Q: What does viral disease depend on? (2)
A: how much the replication the virus undergoes
(also affected by other factors such as host response)
balance between virus virulence and host response
Q: What are the 5 patterns of viral infection?
A: Acute - followed by viral clearance (infects person for a few days then moves on)
Persistent - transforming (stays in body/ alters cells its in to allow it to stay longer)
latent reactivating
slow
Oncogenesis - affect the way our cells control themselves
Q: Draw 4 diagrams for the patterns of viral infection.
A: refer
Q: Draw and label a diagram for a typical acute infection.
A: ph curve one: duration of infection (x) and virus growth (y)
->entry of virus
innate defence
establishment of infection
induction of adaptive response
adaptive response
->virus cleared
memory
lower section- threshold level of virus required to activate adaptive immune response
Q: 2 examples of acute infection that are asymptomatic. What provides immunity? Continue to circulate?
A: Colds and influenza
Adaptive immune response provides immunity (usually life long against that particular strain)
viruses continue to circulate in populations by antigenic variation
Q: 2 examples of acute infection that are not so mild. Infection of? Mortality rate? What do viral growth factors induce?
A: Smallpox and Dengue
skin
20-80
proliferation of skin resulting in pox
Q: Name 2 acute infections with accidental pathogenesis.
1: transmission and symptoms
2: symptoms
A: virus has been and gone but left change
Polio - faecal oral route causing localised infection of small intestine-> infects motor neurones and can cause paralysis
Rubella - causes mild rash except in early stage fetus where virus has strong tropism for dividing neuronal tissue -> Leads to classic triad:
Deafness
Eye abnormalities (cataracts)
Congenital heart disease
Q: What are the 2 types of persistent viral infections? 3 examples.
A: Chronic - low level replication of viruses in tissues which regenerate (EXAMPLE: papillomaviruses in warts)
Latent reactivating - viral genomes are maintained but no virus is seen until episodes of reactivation at times at which you are immunocompromised.
EXAMPLE: herpes simplex, varicella zoster
(burst out from nerve ending near to skin-> replicate in skin)
Q: What are the strategies of viral persistence? (3 and examples)
A: There are lots of accessory genes which allow viruses to evade our immune responses.
Evading immune surveillance: MHC Downregulation- can’t present peptide etc derived from virus: eg Human Cytomegalovirus (HCMV)
CTL escape by mutation - Hepatitis C virus
Infecting tissues with reduced immune surveillance e.g. CNS: measles SSPE, herpes viruses skin, papillomavirus // top layers of skin where T cells aren’t really surveying
Q: Describe herpes simplex virus in terms of latency.
A: The virus first enters through the skin
primary site of infection: productive infection of epithelium cells
infection by retrograde transport towards cell body
It gets into the nerve and sits there in a latent state (secondary site of infection and site of latent infection: sensory neurone)
When you get reactivation of the virus, it begins to make new copies of itself and travels back to the end of the nerve (anterograde transport) and replicates through the skin (forming a cold sore)
can travel in other direction towards body-> neuroinvasion = serious problem
Q: Neurones don’t divide and they live till you die. Therefore?
A: if nerve gets infected it may contain lots of copies of viral genome and every now and then it will get reactivated -> larger effect over time
Q: Viruses may cause cancer. How? What does this do?
May encode an oncogene -> Interferes with the host cell cycle to enhance their own replication
By making the host cell into a cancer cell, the virus can replicate more and keep moving onto new cells
Q: Provide 4 examples of viruses that cause cancer.
A: Papilloviruses encode inhibitors of tumour suppressor p53, E6 and E7 genes - forces cells into S phase
Kaposi Sarcoma-Associated Herpes Virus (KSHV or HHV8) and Merkel Cell Polyoma were discovered by finding non-human genetic material in tumours
HTLV-1 (retrovirus) causes adult leukaemia
Q: Hepatitis B and C can cause which type of cancer? How many carriers of HBV? How many annual deaths?
A: hepatocellular carcinoma (liver)
350 million carriers of HBV
600,000 annual deaths
HCV is a
Q: What is HBV? Genome? Uses what during life cycle? Transmitted through? Vaccine?
A: hepadnavirus (has a DNA genome) but it uses reverse transcriptase during a stage in its life cycle
Transmitted through blood and semen
There is a vaccine
Q: What type of virus is HCV? What percentage of people with HCV will go on to get hepatocellular carcinoma? What’s improved?
A: blood borne virus
4% of people
antiviral therapies
Q: What is the Epstein-Barr Virus? How many of us are infected with it? In most people, it causes? then? Passed on via? also called? 2 other conditions associated with it? What does incidence suggest?
A: gamma herpes virus - most common virus infection of mankind
95%
in most people it causes a lytic infection in childhood or infectious mononucleosis in young adulthood. and then remains latent in B cells
passed on in saliva
also causes Burkitt’s Lymphoma
Some people infected with EBV will go on to develop cancer (combined with other circumstances):
Hodgkin’s Lymphoma
Nasopharyngeal Carcinoma
incidence of these varies geographically suggesting other predisposing factors to these outcomes
Q: What does the outcome of infection vary depending on? (8)
A: Viral sequence
Virus load
Host immune repsonse/status
Host co-morbidity
Co-infections
Other medications
Host genetics
Host age/gender
(mainly virulence and host response)
Q: Explain how viral sequence can have an impact on varying virulence in the polio virus.
A: Two strains of polio virus may vary in virulence
One mutations may turn it into a live attenuated virus
Another mutation may make it invade the motor neurone and cause paralysis
Q: Explain the impact of viral load in terms of chicken pox.
A: The first child in a family to contract chicken pox often has a milder illness
This may be because the second child is in closer contact to an infected individual and hence gets infected by a higher dose
Q: What are 2 examples of co infections?
A: HHV8 causes Kaposi Sarcoma in HIV infected individuals
Hepatitis Delta Virus (a small defective RNA virus) only infects people with HBV infection - it suppressed HBV replication and causes severe liver disease with rapid progression to cirrhosis and hepatic decompensation
Q: Describe 3 examples of genetic resistance from viruses (susceptibility too).
A: Genetic Resistance and Susceptibility
A: CCR5 delta 32 mutation protects against HIV-1 infection
Killer-cell immunoglobulin-like receptor (KIRs) can determine the outcome of a hepatitis C virus infection
Interferon-induced transmembrane protein 3 (IFITM3) was associated with a severe outcome in 2009 H1N1 pandemic
Q: List co morbidities and conditions for severe influenza. (7)
A: Asthmatics and respiratory viruses
Obesity (chronic inflammatory condition)
Immunosuppression
Immunodeficiency
Elderly
Diabetes Mellitus
Pregnancy
