Lecture 11 - Parvo and Adeno Viruses Flashcards
What is the smallest DNA virus?
Parvo viruses
4 parvo virus geni?
- Genus Erythrovirus
- Genus Dependovirus (Adeno-associated viruses)
- Genus Densovirus (Insect viruses)
- Genus Bocavirus
2 examples of genus Erythrovirus parvo viruses?
- B19
2. RA-1
Which only 2 parvo viruses can cause disease in humans? What does each cause?
- B19: causes erythema infectiosum, aplastic crisis, and also associated with acute polyarthiritis
- Bocaviruses: causes acute respiratory disease and infection may be severe in children
What do adeno-associated parvo viruses require for replication?
Require a helper virus for replication usually an adeno virus
7 unique properties of parvo viruses?
- Smallest DNA viruses
- Naked icosahedral nucleocapsids (no envelop)
- Single stranded +/- sense DNA with ends of the genome having inverted repeats that hybridize to form hairpin loops => primer for DNA synthesis
- Remain viable even after storage for years
- Can establish latent infections
- Dependoviruses (AAV) require coinfection with adenoviruses, herpesviruses, or poxviruses
- Erythrovirus replication tends to be dependent on helper functions supplied by rapidly growing cells
Where does the name bocavirus come from?
Bovine + canine
Describe the infection of a fetus with B19.
- First trimester: often ends with death
- Second trimester: infection => Hydrops fetalis
- Third trimester: no clinical findings
Describe latently parvo virus infected cells.
Cells latently infected possess integrated parvovirus genomes but are not transformed and have no change in phenotype and non are oncogenic
What is erythrovirus replication dependent on? Implication?
Tends to be dependent on helper functions supplied by rapidly growing cells => found associated with tumors and possess oncolytic properties
What 2 parvo viruses infect humans without causing disease?
- Erythrovirus Lu-111/RA-1
2. Dependovirus AAV serotype 1, 2, 3, and 5 (antibodies prevalent)
How does the B19 parvovirus replicate? 3 steps
- Virus infects progenitor endothelial and placental cells that are mitotically active and express the erythrocyte P antigen through coated pits (on fetal liver and heart, bone marrow, leukemic cells)
- Internalized parvovirus delivers its genome to nucleus where the single-stranded DNA is uncoated and converted to double-stranded DNA by host factors and DNA polymerases only present in growing cells
- Transcription, replication, and assembly occur in the nucleus (translation occurs in cytoplasm to make structural and nonstructural proteins)
- Virus is released by cell lysis through nuclear and cytoplasmic membrane degeneration
Other name for erythrocyte P antigen?
Globoside
Are individuals who lack the P antigen on target cells susceptible to the B19 parvovirus?
NOPE
Transmission routes of parvovirus B19?
- Respiratory droplets
- Oral secretions
- Vertically from mother to fetus
What is important to note regarding the contagious period of the parvovirus B19?
Contagious period precedes symptoms
How does the parvovirus B19 infect a fetus?
It can cross the placenta
What is the parvovirus B19 resistant to? Why?
Inactivation due to its capsid
Who is at risk of parvovirus B19 infection? 4
- Children, especially those in elementary school for erythema infectiosum
- Parents of children with B19 infection
- Pregnant women
- People with chronic anemia for aplastic crisis
Other name for erythema infectiosum?
5th disease
Location of B19 parvovirus?
Worldwide
When is 5th disease more common?
Late winter/spring
Modes of control of B19 parvovirus infections?
NONE
Viral 4 CPE manifestations following B19 pirovirus infection?
Changes in erythroid precursors
- Cytoplasmic giant pronormoblasts in bone marrow
- Pseudopod formation
- Vacuolization
- Margination of nuclear chromatin
% of B19 infections that are asymptommatic?
20-50%
Symptoms of parvovirus B19 infection?
- Mild influenza-like illness (fever, headache, chills, myalgia, malaise)
- Erythema infectiosum
- Transient aplastic crisis in people with chronic anemia (n hemolytic anemia or sickle cell anemia)
- Arthropathy (acute polyarthritis: symptoms in many joints) usually in women lasting for 2 weeks
- Hydrops fetalis: anemia-related pathology
Does hydrops fetalis cause congenital anomalies?
NOPE
Why does the B19 parvovirus cause erythema infectiosum?
- Virus infection of endothelial cells in blood vessels causes a bright red rash associated with erythema infectiosum
- Immune complexes are also responsible
Does B19 parvovirus infection spread to blood?
YUP => viremia
Immune response to B19 parvovirus infection?
Antibody response is important for resolution and prophylaxis
Describe erythema infectiosum. What to note?
Biphasic disease:
- Initial phase is related to viremia and lytic infection => flulike symptoms and viral shedding
- Later phase is non-infectious and related to the immune response => circulating immune complexes of antibody (IgM + IgG) => erythematous maculopapular rash, arthralgia, and arthritis
NOTE: after the initial phase the virus is very difficult to isolate from any site
Why does B19 parvovirus infection lead to aplastic crisis in people with chronic anemia?
Due to the depletion of erythroid precursor cells and the destabilization of erythrocytes
Effect of B19 parvovirus infection on individual without chronic anemia?
Slight drop in hemoglobin level
B19 incubation period?
6 days
During what phase of erythema infectiosum is the B19 virus in the throat?
Initial infectious phase
5 symptoms of erythema infectiosum?
- Slapped cheeks: bright red rash on the cheeks
- Low grade fever
- Runny nose (coryza)
- Sore throat
- Rash with small red spots on the extremities with lacy appearance
What are the 4 lab diagnostic techniques for B19 infections?
IgM or viral DNA must be detected (to distinguish the rash of B19 from that of Rubella in pregnant woman):
- ELISA for B19 IgG and IgM
- B19 viral detection from throat swabs
- Viral DNA by PCR in blood
- Fetal infection by PCR of amniotic fluid
What are the 4 unique features of adenoviruses?
- Naked icosahedral capsid with tail fibers (viral attachment proteins) at vertices, which attach to cells and start the replication cycle
- Human adenoviruses are subgrouped A through G by DNA homologies and by serotype (more than 55 serotypes)
- Serotypes are mainly due to differences in the penton base and fiber proteins, which determine the nature of tissue tropism and disease
- Virus causes lytic, persistent, and latent infections in humans, and some strains can immortalize certain animal cells
Describe the structural proteins of adenoviruses.
Hexons and pentons, some of them containing group or family antigens and some serotyping antigens
5 capsid structural proteins of adenoviruses? Describe each.
- Hexon protein II: contains group or family antigen and some serotyping antigens
- Penton base protein III: toxic to tissue culture cells
- Fiber IV: responsible for attachment and hemagglutination and contains some serotyping antigens
- Hexon and penton-associated proteins (6, 8, 9, and 3a)
2 core structural proteins of adenoviruses? Describe each.
- Core protein 1 DNA-binding protein
2. Core protein 2 DNA-binding protein
How are human adenoviruses classified?
Classified into subgroups A-G based on:
- Hemagglutination groups
- Serotypes
- Oncogenic potential (although transformation in tissue culture is not a differentiating factor)
- % G-C in DNA
Role of E1B protein of adenovirus type 2?
Protects cell from lysis by TNF
Role of VA protein of adenovirus type 2?
Prevents INF inhibition of protein synthesis
Role of 2 E3 proteins of adenovirus type 2?
- E3 codes for proteins that bind to heavy chain of Class I MHC preventing transport to the surface
- Another E3 protein protects cells from lysis by TNF
Do adenoviruses infections lead to last immunity to re-infection with the same serotype? What to note?
YUP
NOTE: this is in contrast to most respiratory viral infections
Are fetuses protected by maternal antibodies against adenoviruses?
Maternal Ab generally protect infants up to age 6 months against severe lower respiratory disease
What % of human viral infections are by adenoviruses? What to note?
5-10%
NOTE: most occur in childhood:
- 75% before age 15
- 50% before age 5
Where are most adenovirus infections located?
Respiratory and eye infections
How are adenovirus infections transmitted? Which ones apply to pharyngeal infections?
- ***Respiratory droplets (aerosol)
- ***Close contact
- ***Fecal-oral route: family studies have indicated large numbers of adenovirus particles can be shed in feces (10^11 particles per gram) and can infect half of all susceptible members in the same family
- Can persist for weeks on environmental surfaces, swimming pools (PCF), and poor aseptic techniques (EKC)
% of adenovirus infections that are asymptommatic?
50%
Do all adenovirus serotypes cause disease?
NOPE (fewer than half of the 55 serotypes cause disease)
How are adenovirurses transmitted from pharyngeal infection to eyes?
Fingers
Mechanism pathway of adenovirus infection?
- Virus infects mucoepithelial cells in the respiratory tract, gastrointestinal tract, and conjunctiva or cornea => causing cell damage directly
- Virus persists in lymphoid tissue (tonsils, adenoids, Peyer’s patches)
- Antibody is important for clearance
What does the disease caused by adenovirus infections depend on?
Disease is determined by the tissue tropism of the specific group or serotype of the virus strain
7 illnesses caused by adenoviruses? Indicate the most common serotypes for each.
- Endemic respiratory disease (1, 2, 5)
- Acute respiratory disease (ARD) of military recruits (3, 4, 7, 14, 21) and children
- Adenoviral pneumonitis (3, 4, 7b, 14, 21)
- Epidemic keratoconjunctivitis (8, 19, 37)
- Pharyngoconjunctival fever (3 in kids, 7)
- Genitourinary infections (37, 11)
- Enteric infections (40, 41)
Describe endemic respiratory disease caused by adenovirus infection.
Constantly present in a particular locality and persists asymptomatically for years in tonsils and adenoids and virus can shed continuously in feces
Mechanism of persistence uncertain, perhaps replication is held in check by antibody synthesized by these lymphoid organs
What adenovirus subtypes cause acute respiratory disease in children? What does each cause?
- B: causes epidemics and sporadic cases
- C: causes sporadic mild respiratory illness of infants and children and can establish latent infection in tonsillar tissue
What % of all acute respiratory diseases in children less than 5 yr old are associated with adenovirus?
5%
What serotype causes adenovirus pneumoniae? What to note?
Serotype 7
NOTE: can be fatal
What serotypes of adenoviruses are seen in daycare centers and orphanages?
Serotypes 5 and 7
What is the primary cause of morbidity among military recruits? What to note?
ARD
NOTE: epidemics usually peak at 3-6 weeks after onset of training
When does ARD have higher incidence in the military?
Winter and spring
Symptoms of ARD in the military?
- Infection can be as a mild respiratory disease with symptoms of sore throat and cough, sometimes coryza, headache, and chest pain
- Malaise
- l0% of sick recruits will develop pneumonia
For how long does ARD in military recruits last?
10 days
What adenovirus serotypes cause ARD epidemics in the military?
Serotypes 4 and 7
What is the high incidence of pneumonia due to ARD in the military due to?
Could be due to close living quarters of individuals from different geographic areas and backgrounds and subjected to crowding conditions and stress
Vaccine available to military against adenoviruses?
Live attenuated vaccine containing serotypes 4 & 7 is available to the military ONLY
Where was epidemic keratoconjunctivities first described? What was it called? How was it transmitted?
Described in World War II when ship building flourished, originally called Shipyard’s eye
Transmission probably took place in medical facilities, where workers sought treatment for foreign bodies and chemical irritation of their eyes
Incubation period for epidemic keratoconjunctivitis?
8-10 days
7 symptoms of epidemic keratoconjunctivitis?
- Conjunctivitis (pink eye) that may be follicular (FIRST)
SECOND
- Edema of the eyelids
- Pain
- Photophobia
- Lacrimation
THIRD
6. After a couple of days, superficial erosions of the cornea may develop
FOURTH
7. Full-blown case characterized by deeper subepithelial corneal infiltrates in the center of the cornea => may interfere with vision and can cause lasting visual impairment
Are both eyes infected in epidemic keratoconjunctivitis?
Usually not
What are outbreaks of epidemic keratoconjuctivitis centered around?
Seem to center around industrial settings and eyecare facilities with spread by contaminated instruments, fingers, eye solutions, and ointments as well as ocular trauma
Symptoms of pharyngoconjunctival fever?
- Pharyngitis
- Conjuntivitis (pink eye) of one or both eyes
- Spiking fever
- Diarrhea, coryza, and otitis may be present
- Tonsils show an exudate and lymphadenopathy is often observed
What are outbreaks of pharyngoconjunctival fever centered around?
Centered around summer camps, swimming pools and lakes with inadequate chlorination of water
3 modes of transmission of pharyngoconjunctival fever>
- Direct contact with contaminated water
- By respiratory route
- Secondary spread of the virus into a family is often seen
Incubation period of pharyngoconjunctival fever?
6-9 days
How to test for adenovirus causing epidemic keratoconjunctivitis??
- Immunofluorescence microscopy of eye specimens
2. Culture in cultured human kidney cells
What genitourinary infections are caused by adenoviruses?
- Cervicitis and urethritis are common manifestations of venereal infection with type 37, which was first identified in prostitutes
- Cystitis seen mainly in young boys is caused by type 11. In acute hemorrhagic form, cystitis is characterized by hematuria and dysuria.
How do adenoviruses cause genitourinary infections? In what individuals?
Adenoviruses commonly establish asymptomatic persistent infections of the kidney and may shed virus in urine for months or years
This is observed in immunocompromised individuals, such as renal transplant patients
What enteric infections do adenoviruses cause?
- Gastroenteritis (sometimes associated with respiratory symptoms and conjunctivitis)
- Necrotizing enterocolitis
What % of infant diarrhea is caused by adenoviruses?
5-12%
What is the adenovirus capsid resistant?
Resistant to inactivation by GI tract and drying
Where are adenovirus infections found?
Worldwide
How to diagnose adenovirus infection?
Isolation of virus from tissue culture and detection of a 4-fold or greater rise in antibody titer (CF and HAI are routine)
What is killer adenovirus 14?
Sequence of the fiber gene showed a 6 base pair deletion resulting in a 2-amino acid deletion, Lysine to Glu in the knob region
More virulent AD14 first appeared in 2006 at a military base and was slightly different from the original AD14 1955 strain
