M: Virology 3 - Week 11 Flashcards
Name 2 DNA viruses that can cause conjunctivitis
Adenovirus
Molluscum contagiosum
(also HSV and VSV but they are less important to remember)
Name 2 RNA viruses that can cause conjunctivitis
Enterovirus 70
Coxsackie virus 24
What type of cconjunctival infection is the most common?
viral conjunctivitis
Where does viral conjunctivitis typically occur? (i.e. source of the infection)
Upper respiratory tract
Are lymphoid follicles common or rare in viral conjunctivitis?
common
Where do adenoviruses start? Where can they spread to and replicate? (3)
Start in glandular tissue. Can spread to conjunctiva, pharynx, GIT
In regards to Adenoviruses, describe:
A: Capsid symmetry
B: Are they enveloped or non-enveloped?
C: Where are their fibres located?
A: Icosahedral
B: non-enveloped. Therefore are hardy
C: at their apices
What conditions can adenovirus cause? (4)
ocular conditions (e.g. conjunctivitis)
respiratory
genital
GIT disease
What virus is considered the most common cause of viral conjunctivitis?
Adenoviruses
How may adenovirus ocular infections present? (2) What adenoviruses are responsible for each presentation?
Pharyngeal conjunctival fever (PCF) - adeno 3, 4, 7 Epidemic keratoconjunctivis (EKC) - adeno 8, 19, 37, others
Why are adenoviruses difficult to disinfect against?
Because they are non-enveloped
Describe the following features of adenoviruses:
D: how contagious are they?
E: how robust are they?
F: how long is their incubation period?
D: Highly contagious
E: Highly robust; survives in environment
F: Incubation period = 4-18 days long
Describe the following features of adenoviruses:
G: How long do they survive on fomites?
H: Where are particles shed from (2) and for how long? (1)
G: 8-35 days
H: particles are shed from nasopharynx and tears for 2 weeks
List 3 (out of the 11) symptoms of epidemic keratoconjunctivitis (EKC)
frequent dull pain, photophobia, reduced VA [important]
preauricular or submandibular adenopathy [important?]
significant periorbital lid edema
Marked conjunctival hyperemia, chemosis
Petechial haemorrhages common
Superficial punctate keratitis
Subepithelial infiltrates 1-2 weeks after onset
Why can epidemic keratoconjunctivitis (EKC) present with submandibular adenopathy?
because adenoviruses are also replicating in glandular tissue such as submandibular glands
How long after the onset of epidemic keratoconjunctivitis (EKC) do subepithelial infiltrates occur?
1-2 weeks after onset
How long may subepithelial infilrates last in people with epidemic keratoconjunctivitis (EKC)?
weeks or months
What age group is pharyngeal cconjunctival fever (PCF) predominantly seen in?
children
What are midwinter epidemics of PCF due to? (1)
respiratory infections
What are summer episodes of PCF associated with?
swimming pools
Describe the following features of PCF:
A: unilateral or bilateral?
B: list 6 other symptoms
A: can be either unilateral or bilateral B: tearing fever preauricular adenopathy pharyngitis occasional superficial punctate keratitis subepithelial infiltrates
In terms of preauricular adenopathy, how are EKC and PCF differentiated?
EKC: is tender
PCF: is not tender
Describe the pathogensesis (in terms of replication) of adenoviruses in 4 steps
- Bind well to CAR on mucosal epithelium
- Enter cell via RME through clatherin coated pits
- Acidification in the endosome modifies the capsid proteins
- This allows release into cytoplasm and transport via microtubules to the nucleus for replication
What does CAR stand for?
cell adenovirus receptor
What contributes to the pathogenesis of adenovirus after replication? (3)
Release of new virions result in cell lysis (i.e. a cytotoxic virus)
Some gene products suppress killing by cytotoxic T cells, so infection persists, stimulating large infiltrates of T and B cells
Even after infection is cleared, persistant infiltrates may lead to loss in VA for weeks to months
How can we manage adenovirus infections? (4)
Supportive treatment (compresses, other pain relief, etc.) Instruct re-scrupulous handwashing to prevent spread Anti-inflammatory agents to reduce infiltrates (e.g. NSAIDs) Topical steroids (controversial, but consider for severe EKC)
Are there any specific anti-virals for adenovirus infections?
No
In regards to Enteroviruses, describe the following:
A: What family of viruses do they belong to?
B: What is their capsid symmetry?
C: How big are they?
D: Are they enveloped or non-enveloped?
A: picornaviridae
B: Icosahedral
C: Small
D: Non-enveloped
Name the 2 subtypes of enteroviruses that are ocular pathogens
Enterovirus 70
Coxsackie virus 24
In what age groups do we see enterovirus infections? (2)
children and young adults
In regards to Enteroviruses, describe the following:
E: How contagious are they?
F: How long is their incubation period?
G: How are they transmitted? (2)
E: Highly contagious
F: Rapid (24 hours)
G: Fingers and Fomites (i.e. optometrists)
What proportion of enterovirus infections involve subconjunctival hemorrhages?
80%
Describe the course and recovery of enteroviruses (2)
rapid course with uneventful recovery
Can enterovirus infections present with a severe presentation?
yes
What symptoms do enterovirus infections present with? (3)
Sensation of burning or foreign body
Eyelid swelling
Photophobia
How can you manage enterovirus infections? (3)
Supportive treatment (compresses, other pain relief, etc.) Instruct re-scrupulous hand washing to prevent spread Topical NSAIDs
What family of virus does molluscum contagiosum belong to?
poxviridae
How does molluscum contagiosum affect the eye? (2)
chronic follicular conjunctivitis in association with an irritative eyelid lesion (nodules)
How is Molluscum contagiosum transmitted (in the eye)?
by direct contact with nodules
What is the incubation period of molluscum contagiosum in the eye?
14 to 50 days
What viruses can cause keratoconjunctivitis or keratitis? (3)
Adenovirus
HSV (herpes simplex)
VZV (varicella zoster)
In regards to Herpesviruses, describe the following: A: Capsid symmetry B: Enveloped or Unenveloped? C: How many types? D: How long can they be latent?
A: Icosahedral
B: Enveloped
C: 8 types
D: all types can establish life-long latency
What are the 2 serotypes of HSV?
HSV-1 and HSV-2
How do you distinguish between HSV-1 and 2? (2)
Serological tests (detect antigens) OR PCR (detects genes)
What symptoms can both types of HSV cause? (2)
localised infections (e.g. cold sores, blepharoconjunctivitis, conjunctivitis, keratoconjunctivitis, keratitis, uveitis, genital herpes) AND disseminated infections (encephalitis, mengoencephalitis, etc.)
What symptoms are predominantly caused by HSV-1? (compared to HSV-2) (6)
cold sores blepharoconjunctivitis conjunctivitis keratoconjunctivitis keratitis uveitis
What symptoms are predominantly caused by HSV-2? (compared to HSV-1) (1)
genital herpes
In terms of the entry of HSV, describe the following:
A: How is HSV acquired?
B: What are the target cells (3)
C: Name a particularly susceptible site
A: by direct contact of infected saliva (HSV-1) or other secretion
B: Epithelial cells, Fibroblasts, Macrophages
C: Mucous membranes
How does the entry of HSV work? (in terms of binding) (2)
Glycoproteins on envelope bind cell surface receptors
Binding triggers fusion of the envelope with the cell membrane and allows release of the nucleocapsid into the cytoplasm
In regards to replication of HSV in epithelial cells:
A: How much virus is produced?
B: Is the virus efficiently released? Where?
C: How infectious is it?
D: Is it symptomatic or asymptomatic
A: Large amounts of infectious virus
B: NOT efficiently released into intercellular space
C: Highly
D: May be asymptomatic
In regards to HSV replication in epithelial cells: what leads to the infection of nerve cells in the trigeminal ganglion? (3)
infection of any of the ophthalmic, maxillary and mandibular branches of cranial nerve V by infected epithelial cells
What causes the latency of the HSV?
When HSV is maintained as an episome in ganglia (no replication)
How may recurrent HIV infections occur (at the original site)?
via reactivation from ganglia (in response to various stimuli such as stress
What does HSV infection of epithelial cells result in? (5)
rapid virus multiplication apoptosis spread vesicle formation infection of sensory neurons
Describe the process of establishment of latency in HIV (2 steps)
- HSV infection of epithelial cells
2. Axonal transport to dorsal root ganglion
What does axonal transport to the dorsal root ganglion achieve?
results in latent infection, the virus genome being maintained as an episome
What is an episome?
a genetic element inside some bacterial cells, especially the DNA of some bacteriophages, that can replicate independently of the host and also in association with a chromosome with which it becomes integrated.
Which ganglia do HSV1 and HSV2 typically go to when establishing latency? (2)
HSV-1: trigeminal ganglion
HSV-2: sacral ganglion
Describe the process of reactivation of HSV (3)
- Certain stimuli and immunosuppresion induces reactivation of HSV from the episomal state
- Virus is transported down the sensory nerve
- Reinfection at the mucocutaneous site: results in a fresh outbreak of vesicles or asymptomatic shedding
Name stimuli that might induce reactivation of HSV (5)
fever sunlight UV light stress menstruation
During the reactivation process of HSV, how is the virus transported?
is transported down the sensory nerve
What does reinfection of HSV at the mucocutaneous site result in?
a fresh outbreak of vesicles or asymptomatic shedding
What associated conditions can primary infection of HSV-1 cause? (3)
stomatitis
blepharitis
conjunctivitis (typically unilateral)
Is recurrent eye disease after initial HIV infection common?
Yes. Rates of recurrence after initial infection are currently 10% at 1 year and 60% at 2 years
What is the most common cause of corneal blindness in the developed world?
HSV keratoconjunctivitis, keratitis
How common are posterior segment diseases resulting from HSV infection?
Rare
How can you manage HSV infection? (4)
Antiviral therapy: to prevent/reduce lesions
Prophylactic oral acyclovir, valacyclovir, or famciclovir
Physical barriers to reduce spread
No effective vaccines yet
How can treatment with propylactic oral acyclovir, valacyclovir, or famciclovir affect HSV infection? (2)
significantly reduces the risk for recurrent HSV eye disease and adverse ocular events from HSV
What does primary infection by VZV cause?
Chickenpox
In regards to the pathogenesis of VZV:
A: What happens on day 0? (2)
Day 0:
Infection of the conjunctiva and/or URT mucosa
Viral replication in regional lymph nodes
In regards to the pathogenesis of VZV:
B: What happens on day 4-6? (3)
Days 4-6:
Primary viraemia in blood circulation
Further viral replication in liver and spleen
Secondary viraemia
In regards to the pathogenesis of VZV:
C: What happens on day 10? (1)
Day 10:
Infection of skin and vesicular rash
What can recurrent infection of VZV cause? (1)
painful blisters of shingles that follow a dermatome
How can you manage VZV infection?
Minimise corneal damage and scarring
Antiviral therapy (oral acyclovir, valacyclovir, famciclovir)
Prevent spread by good hygeine
VZV vaccine
Name 2 viruses that can cause congenital retinitis/chorioretinitis during/post delivery of the child
HSV and VSV
Name 2 viruses that can cause congenital retinitis/chorioretinitis after transplancental transmission
Cytomegalovirus
Rubella Virus
In regards to Rubella virus: A: What condition does it cause? B: What virus family does it belong to? C: Is it enveloped or unenveloped? D: How long is the incubation period?
A: German Measles
B: Togaviridae
C: Enveloped
D: 18 day incubation period
In regards to Rubella virus:
E: is it a DNA or RNA virus?
F: How does it affect the skin?
E: RNA virus
F: pink erythematous rash on the face and limbs
In what trimester of pregnancy does congenital rubella syndrome typically occur?
first trimester
How does rubella affect foetal development? (2)
slows down rate of cell division
babies are small and development of key organs in first trimester is impaired
Name 3 conditions that congenital rubella syndrome might cause
Retinitis
Chorioretinitis
Cataracts
How can you prevent infection with rubella?
Rubella vaccine
In regards to cytomegalovirus:
A: What virus family is it in?
B: Is it typically symptomatic or asymptomatic?
C: How is it spread? (3)
A: Herpesviridae
B: Typically causes asymptomatic infection (occasionally glandular fever)
C: Spread by - close personal contact, blood, transplanted tissues
In what population does symptomatic infection of cytomegalovirus occur?
in immunosuppressed people (e.g. HIV, transplant patients)
Can cytomegalovirus cause congenital infection?
Yes. It is an important cause of congenital infection
Does cytomegalovirus target one or multiple organ systems?
Targets multiple organ systems, including the eye
What does reactivation of cytomegalovirus (CMV) cause?
CMV retinitis
How can you manage CMV retinitis? (3)
Ganciclovir I.V
Intravitreal/oral valganciclovir
HAART for HIV patients
Name 6 viruses that cause viral eye infections?
Adenovirus Enteroviruses HSV VZV Cytomegalovirus Rubella Virus