Family: Poxviridae Flashcards
What are the 2 subfamilies of Poxviridae?
- Chordopoxviridae - Avipoxvirus, Capripoxvirus, Leporipoxvirus, Orthopoxvirus, Parapoxvirus, Suispoxvirus, Yatapoxvirus,
- Entomopoxviridae - Alpha/Beta/Gammaentomopoxvirus
Who was Edward Jenner?
pioneer in the field of vaccinology who discovered the concept of a smallpox vaccine by identifying the link between cowpox nodules on the udder of cattle and the milker’s nodules
What are the 3 first novel criteria of small poxvirus?
- first disease to be irradicated
- first virus to have some effective antiviral therapy
- first vaccine developed
What is the most complex family of viruses that infect various species of vertebrate?
Poxviridae
Where on the embryonated chicken egg does Poxviridae grow? How do they affect the egg?
chorioallantoic membrane
produce pock lesions
Where in the cell does poxvirus multiply? What organ does it prefer to replicate in?
replicate in the cytoplasm and produce intracytoplasmic inclusion bodies
epidermis
What are the 2 species of smallpox? What is the earliest evidence of existence of smallpox?
(no animal reservoir)
1. Variola major (20% mortality)
2. Variola minor (1-2% mortality)
Egyptian mummies - Ramses V
What type of genome does Poxviridae have? What is the overall structure of the virus?
among one of the largest dsDNA, linear viruses
brick shaped, with a complex symmetry consisting of a core and 2 lateral bodies
In what kind of solution do members of Poxviridae tend to aggregate?
high salt solutions
What do members of Poxviridae tend to be resistant to? Sensitive to?
trypsin
ether
common detergents, formaldehyde, and oxidizing agents
In what conditions is Poxviridae most stable in? What temperature is it most sensitive to?
dry conditions at room temperature
temperatures greater than 40 C
Does lyophilization affect the infectivity of Poxviridae?
no
Poxviruses infecting humans are all zoonotic except what 2 viruses?
- molluscum contagiosum virus (MOCV)
- orthopoxvirus variola virus (VARV) - the etioloigc agent of smallpox
What plays a major role in the clearance of vertebrate Poxvirus infections?
neutralizing antibodies and cell-mediated immunity
(reinfection rates are generally low and less severe)
How does previous infection with small poxvirus affect the immune system?
those previously infected are generally immune to the disease for the rest of their lives
What is the pathogenesis of Poxvirus?
- infection starts through inhalation of the small poxvirus in the upper respiratory tract, where it is able to multiply, and the virus disseminates through the lymphatic and cell-associated viremic spread
- hemorrhage of small vessels in the dermis leads to rash and “pox”
What are the Poxvirus infection stages of lesion development?
- exposure
- 12 days average incubation period
- 2-4 days of prodrome (early signs of infection)
- macules —> papules —> vesicles —> pustules —> scabs
What is the genome structure and organization of Poxviridae?
single molecule of linear dsDNA about 130-300 kb
(encodes 200 proteins, 100 of which are contained in virions)
What makes Poxviridae different compared to other DNA viruses?
replicates in the cytoplasm
(most DNA viruses replicate in the nucleus)
What are the 5 steps of the Poxvirus infection cycle?
- entry and release of core
- early mRNA synthesis products are released from core, which causes cell proliferation and local immune suppression
- DNA is synthesized for packaging and as a template for intermediate gene expression (transcription specificity factors for late gene expression)
- transcription and translation of late, structural protein genes, assembly of particles at Golgi, and release on cell lysis or infection of adjoining cells
- Poxvirus release by exocytosis
What is the mechanism behind Poxvirus release by exocytosis?
immature virion (IV) is formed from the Golgi and matures to form an infectious intracellular mature virion (IMV), which acquires another membrane to form an intracellular enveloped virion (IEV) that can be transported to and fuse with the plasma membrane
What is characteristic of the orthopoxvirus cow poxvirus infection?
papular, pustular, and crusty exudative lesions on the udder and adjacent areas of the skin
How does cowpox virus spread through herds? What can serve as a reservoir?
milking of each cow with improper sanitization
rodents —> contagious to humans, cats, and other species
What is the most important of all pox diseases of domestic animals? Why?
capripoxvirus, affecting sheep and goats of all ages
high mortality in young animals and significant economic loss caused by a decrease in milk production and damage to the quality of hides and wool
How is capripoxvirus transmitted?
- direct contact**
- indirect by contaminated environment
What is the incubation period of capripoxvirus? What are 4 common symptoms?
4-8 days
- hyperthermia
- increased respiratory rate
- eyelid edema
- mucous discharge from nose
How do animals infected with capripoxvirus tend to stand? Where do lesions tend to be most obvious?
with an arched back
areas of skin where the wool/hair is shortest, like the head, neck, ears, axillae, and under the tail
How do the cutaneous nodules from capripoxvirus develop?
- develop widely over the body
- scab and persist for 3-4 weeks
- heals, leaving a permanent, depressed scar
Does capripoxvirus infect humans? How is infection controlled?
no
sanitary prophylaxis nad live/inactivated vaccine
Capripoxvirus:
Where is lumpy skin disease endemic? In what 5 ways does it cause large economic losses?
Africa (reported in Middle East)
- decreased milk production (mastitis)
- abortion
- infertility
- loss of condition (emaciation)
- damaged hides/carcasses
In what 3 ways is lumpy skin disease transmitted? In what conditions does infection increase?
- mechanical biting fly vector
- ingestion of feed and water contaminated with infected saliva
- calves drinking milk from LSDV infected cows
wet summer and autumn seasons
What are 8 major clinical signs of lumpy skin disease?
- pyrexia
- rhinitis - thick/watery nasal discharged
- conjunctivitis/lachrymation
- excessive salivation
- painful nodules developing over the body, particularly in the head, neck, and udder within 7-19 days after inoculation
- depression, anorexia, emaciation
- abortion (fetus may have nodules)
- infertility of bulls due to orchitic and testicular atrophy
Where does lumpy skin virus tend to produce pox lesions? What does this lead to?
mucous membranes of the mouth, alimentary tract, trachea, and lungs
primary and secondary pneumonia
How is lumpy skin disease diagnosed?
viral isolation, ELISA and PCR for viral antigen detection, serological tests - serum neutralization test, fluorescent antibody test
Lumpy skin disease:
all superficial lymph nodes enlarged
In what 3 ways is lumpy skin disease controlled?
- attenuated Neethling strain given to all cattle annually before the summer and rain seasons (calves born to vaccinated cattle remain immune for 6 months)
- disinfection of premises
- proper carcass disposal and burial
What is contagious ecthyma? What causes it?
(contagious pustular dermatitis, orf)
highly contagious, zoonotic, viral skin disease that affects sheep, goats, camels, and other wild ruminants with a worldwide distribution
Parapoxvirus
What do the skin lesions of contagious ecthyma look like?
papules and vesicles on lips, muzzle, inter-digital skin, genitalia, and udder that can progress into pustules and scabs
*can cause anorexia and starvation
How is contagious ecthyma transmitted? Specifically to humans?
direct contact with affected animals and contaminated objects
direct contact of handling affected animals
indirect contact with infected fomites, like wooden fences or wool shears
Where have outbreaks of camel poxvirus been reported? What is this virus closely related to?
Middle East, Africa, Asia
Variola virus —> causative agent of smallpox
What lesions/clinical signs does camel poxvirus infection cause?
- generalized disease
- enlarged lymph nodes
- skin lesions start as erythematous macules and develop into papules, vesicles, pustules, and crusts (1-3 days after onset of fever)
What aged camels are most affected by camel poxvirus? How does it spread? Can it infect humans? Are vaccines available?
younger camels - fatality rate as high as 25%
direct contact and indirect contact via contaminated environment
yes
yes - live attenuated and inactivated
In what animals is Avipoxvirus infection most common?
commercial chickens, turkeys, and other species of pet/wild birds
- decreases egg production
- high mortality rate
What are the 2 forms of Avipoxvirus?
- CUTANEOUS: nodule, wart-like proliferations of hyperplastic epithelium involving the skin of the head (comb, wattles, mouth corners, nostrils, eyes)
- DIPHTHERITIC: proliferative lesions on the mucous membranes extending into the sinus, with involvement of the larynx and trachea, causing dyspnea and rales
What is seen histologically in Avipoxvirus infection?
swollen keratinocytes with eosinophilic intracytoplasmic inclusion bodies
What makes Swinepox virus very hardy? How can it be handled?
can persist in the environment, even in dry conditions
susceptible to most common forms of disinfectants including acid treatment, alcohols, aldehydes, and alkalis
Swine are the natural host for Swinepox virus. Can it infect humans? How is it transmitted? Can recovered animals be reinfected?
no
hog louse, Hematopinus suis, bites
no - they are immune (no vaccines available
How does Swinepox infection present?
classic pox disease - macules progress into papules, vesicles, pustules, and crusts
+/- secondary bacterial infection
What other viruses is monkeypox virus closely related to? What are the 4 main animal reservoirs?
smallpox virus and vaccina virus
- monkeys
- Gambian giant rat
- prairie dog
- African squirrel
How does monkeypox virus spread from animals to humans? How is it transmitted?
PRIMARY INFECTION: animal to human via contact with infected animals or animal product
SECONDARY INFECTION: human to human via contact with infected people and mother to fetus
bites, scratches, consumption of infected meat, close contact with infected respiratory tract secretions or skin lesions
Why is there a great necessity for a comprehensive global surveillance system for monitoring emerging pathogens, like monkeypox, through more advanced approaches?
monkeypox virus is a reverse zoonosis (animal to human, back to animal)
Monkeypox virus disease progression:
How is monkeypox virus infection prevented and controlled?
- no treatment yet
- vaccines (cidofoir, ST-246, Vaccina immune globulin (VIG)) can be used to control outbreak
- JYNEOS vaccine in USA
When are monkeypox virus vaccines most effective? What if it’s given after infection?
- when administered before exposure to the virus
- prevent onset of disease (4 days from exposure)
- reduct symptoms of disease (4-14 days from exposure)
What poxvirus causes infection in rabbits? What are the main 3 symptoms?
Myxomavirus (myxomatosis)
- blepharo-conjunctivitis
- swelling of muzzle and ano-genital region
- subcutaneous gelatinous swellings throughout the body
How does Myxomavirus infection progression compare to other poxviruses?
- virus survives longer and disease progresses longer
- infected animals mostly die within 2-3 days
What is Molluscum contagiosum?
usually benign, mild skin disease characterized by lesions that appear everywhere on the body and typically resolves without scarring within 6-12 months (can last 4 years)
- caused by molluscum contagiosum virus, a poxvirus
What are the inclusion bodies of smallpox virus?
Guarneri bodies
What laboratory techniques can be used to diagnose poxvirus infection?
- proper sampling from affected organs (vesicular fluid, scabs, skin lesions)
- isolation on ECE —> pock lesion on CAM
- microscope detection
- histopathology to identify intracytoplasmic inclusion bodies
- detection of viral Ag (agar gel precipitation test, serum neutralization test)
- detection of viral Ab (ELISA, fluorescent antibody test)
- detection of viral nucleic acid (PCR, rtPCR)***
What type of vaccine is used for smallpox virus today? Is this disease currently a problem?
live attenuated —> vaccina virus
no, declared eradicated in 1980
What are 4 common antiviral therapy for poxviruses? What is each mode of action?
- Istatine-B-thiomeicarbazone - inhibits translation of mRNA
- Methisazone - inhibits morphogenesis
- Rifampin - inhibits morphogenesis
- Codofovir - inhibits viral DNA polymerase synthesis