Infectious diseases: Pathology - Viral infections Flashcards
What type of virus is rhinovirus?
Unencapsulated icosahedral ssRNA
How does rhinovirus induce mucus hypersecretion?
Binds to ICAM-1 on epithelial cells of upper respiratory tract and induces mucus secretion via bradykinin release
Describe the structure of influenza and how this relates to its type and subtype
8 helices of ssRNA
Bound by nucleoprotein which determines the type of virus (A, B, C)
Enclosed by lipid bilayer containing haemagglutinin (HA) and neuraminidase (NA; determines viral subtype H1 to H3 and N1 or N2)
What kind of protection do host antibodies to influenza haemagglutinin and neuraminidase confer?
Antibodies to HA prevent future infection
Antibodies to NA ameliorate future infection
Describe the morphological features of influenza infection
Produces mucosal hyperaemia and swelling with predominantly lymphomonocytic and plasmacytic infiltrate, and mucus hypersecretion
What is the difference between type A and type B/C influenza in terms of their virulence?
Type A is a major cause of pandemics and epidemics, and undergoes antigenic drift and shift
Type B/C mostly infects children, who develop antibodies that effectively prevent re-infection (because these viral types are not subject to antigenic drift or shift)
Explain the difference between antigenic shift and drift
Antigenic drift: mutation of surface HA and NA -> responsible for regional epidemics
Antigenic shift: HA and NA replaced through recombination of RNA segments with animal virus -> responsible for pandemics
What increases risk of bacterial superinfection in influenza? What organisms are typically implicated?
In laryngotracheobronchitis and bronchiolitis, mucociliary function is impaired which increases risk of bacterial superinfection (e.g. pneumococcus, Staphylococcus, Haemophilus)
What are the three mechanisms of immune clearance of influenza?
- Cytotoxic T cells: kill virus-infected cells
- Intracellular anti-influenza protein Mx1: induced in macrophages by stimulation with IFN-alpha and IFN-beta
- Acquired immunity to HA and NA (but not long-lived in influenza A due to antigenic drift/shift)
What type of virus are herpesviruses?
Large encapsulated dsDNA
What is the typical pattern of infection of herpesviruses?
Cause acute infection followed by latent infection with periodic reactivation
How many herpesviruses are there? How are they classified?
8: 3x alpha-group, 3x beta-group, 2x gamma-group
Three alpha-group herpesviruses and the infective syndromes caused by each
- HSV-1: cold sores, herpetic whitlow
- HSV-2: genital sores
- VZV: chickenpox, shingles
Three beta-group herpesviruses and the infective syndromes caused by each
- CMV: asymptomatic (except in utero or in immunosuppression)
- HHV-6: roseola infantum
- HHV-7
Two gamma-group herpesviruses and the infective syndromes caused by each
- EBV: infectious mononucleosis
- HHV-8: Kaposi sarcoma
What cells are infected by alpha-group herpesviruses, and in which cells do they become latent?
Infect epithelial cells
Produce latent infection in neurons (typically dorsal root sensory ganglia)
What cells are infected by beta-group herpesviruses?
Infect variety of cell types
In which cells do gamma-group herpesviruses become latent?
Produce latent infection mainly in lymphoid tissue
Five infective syndromes caused by HSV-1
- Skin/mucosal ulceration (cold sores)
- Herpetic whitlow
- Corneal epithelial damage and blindness
- Encephalitis
- Disseminated in immunodeficiency
Two virulence factors of HSV-1
- Inhibit MHC class I pathways (evade cytotoxic T cells)
- Produce Fc receptors to inhibit complement and evade humoral responses
Six infective syndromes caused by VZV
- Chickenpox
- Shingles
- Interstitial pneumonia
- Encephalitis
- Transverse myelitis
- Necrotising visceral lesions
Where does VZV become latent?
Infects neurons and satellite cells around dorsal root ganglia (most commonly in trigeminal ganglia)
How can VZV cause facial paralysis?
Via infection of geniculate nucleus (Ramsay Hunt syndrome)
Where does CMV become latent?
In monocytes
Describe the morphological features of disseminated CMV infection
- Focal necrosis with minimal inflammation in virtually any organ
- CMV-infected cells exhibit gigantism with large inclusion surrounded by clear halo (“owl’s eye”)
How is CMV transmission dependent on age group?
- Foetus: transplacental
- Neonatal: via birth canal or breastfeeding
- Preschool aged children: saliva
- Adults: venereal (most common), respiratory, faecal-oral
- Iatrogenic: organ transplant, blood transfusion
How does CMV infection present?
In healthy hosts: asymptomatic
In utero: causes cytomegalic inclusion disease (similar to hydrops foetalis)
In immunocompromise: disseminated infection (pneumonitis, oesophagitis, colitis, hepatitis, renal tubulitis, chorioamnionitis, meningoencephalitis)
Seven infective syndromes seen in disseminated CMV infection
- Pneumonitis
- Oesophagitis
- Colitis
- Hepatitis
- Renal tubulitis
- Chorioamnionitis
- Meningoencephalitis
What is the classic genetic derangement seen in Burkitt lymphoma?
8:14 translocation of c-myc oncogene
Burkitt lymphoma is linked to which virus?
EBV
What are five features of clinical presentation of infectious mononucleosis?
- Fever
- Generalised lymphadenopathy
- Splenomegaly
- Sore throat
- Appearance of atypical activated T cells (mononucleosis cells)
Three possible complications of infectious mononucleosis
- Hepatitis
- Meningoencephalitis
- Pneumonitis
Three diagnostic criteria for infectious mononucleosis (in order of greatest to least specificity)
- Lymphocytosis with mononucleosis cells
- Positive monospot
- Specific EBV antibodies
Where does EBV become latent and how?
In B cells, due to EBV proteins EBNA and LMP-1
What type of virus is measles?
ssRNA paramyxovirus
Five examples of paramyxoviruses
- Measles
- Mumps
- RSV
- Parainfluenza
- Human metapneumovirus
Describe the pathogenesis of measles, including the seven infective syndromes/symptoms it produces
Replicates in many cells including lymphoid tissue
Produces viraemia, resulting in dissemination to many tissues
Causes croup, pneumonia, diarrhoea, keratitis, encephalitis, haemorrhagic rash, transient profound immunosuppression
Describe the pathogenesis of the measles rash
Children develop T-cell mediated immunity -> hypersensitivity to viral antigens produces rash
Two rare late complications of measles
- Subacute sclerosing panencephalitis
- Measles inclusion-body encephalitis
What are Koplik spots and for which infection are they pathognomonic?
Ulcerated mucosal lesions near opening of Stensen ducts, pathognomonic of measles
What type of virus is measles?
ssRNA paramyxovirus
What is the function of the two surface glycoproteins of the mumps virus?
- HA/NA activity
- Cytolytic activity
Describe the pathogenesis of mumps virus, including complications
Infects salivary glands (including parotid) and may spread to other sites including CNS, testis, ovaries and pancreatitis
Can cause aseptic meningitis, and sterility due to scarring and atrophy post mumps orchitis
What type of virus is polio?
Spherical nonencapsulated ssRNA enterovirus
What are the two types of polio vaccine and how many strains are included in each?
- Salk (killed) vaccine
- Sabin (oral attenuated) vaccine
Both contain three major strains
What are three reasons polio has been able to be nearly eliminated through vaccination?
- Only infects humans (no other reservoirs)
- Only briefly shed
- Does not undergo antigenic variation
How is poliovirus transmitted?
Faecal-oral route
How does poliovirus present clinically in most cases?
Transient viraemia and fever (or asymptomatic)
What host surface marker does poliovirus bind to?
CD155
How does poliovirus cause paralysis and how often does this happen?
Invades CNS in 1 in 100 infected
Replicates in motor neurons of spinal cord or brainstem motor neurons (causes muscular or respiratory muscular paralysis respectively)
Six infectious syndromes caused by various enteroviruses
- Childhood diarrhoea
- Conjunctivitis: enterovirus
- Rashes: coxsackievirus A
- Viral meningitis: coxsackievirus, echovirus, non-paralytic poliovirus
- Myopericarditis: coxsackievirus B
- Polio: poliovirus
