Poxvirus Flashcards
Poxvirus structural characteristics vaccinia Three strucutral features
vaccinia is prototype for the other poxvirus and has been studied most at the molecular level. Poxviruses are the largest and most complex animal viruses known with dimesnions of 250x350 nm and having an overall oval or brick shape.
Envelope (tightfitting and ether resistant). Biconcave core. and Lateral bodies that fit into the indentations of the bi concave core
Poxvirus structural genome
double stranded DNA with covalently linked termini. It is located inside the core structure of the virus particle.
Poxvirus genetic modification
Within its core, the poxvirus particle can accomodate a genome with additional DNA sequences (genes) artifically or naturally added to its standard genome length.
Vaccinia disease
does not cause smallpox buit may cause its own disease manifestations in certain individuals who are immunocompromised and otherwise impaired.
Vaccinia culture
cultured in embryonated hen’s egg and tissue cultures
chorioallantoic membrane of chick embryo, which produces lesions called pocks
farming vaccainia can be used for bioterrorism or for smallpox vaccine
Vaccinia Replication cycle location
Viral replication in guarnieri bodies.
Vaccinia can replicated entirely in the cytoplasm.
Vaccinia inclusion bodies
guarnieri bodes for small pox virus that correspond to viral replication sites within the cells.
Stages of vaccinia replication: 1 attachment
virus attaches to cell surface recpotrs GAG and is internalized via vacuole formation (viropexis) and therein uncoated through a two step process
Stages of vaccinia replication: 2 uncoating
the virus particle must be disassembled in order to release viral DNA into the cytoplasm of the cell.
First step: host cell enzymes remove outerenvelope and lateral bodies causing distension of core and activation of core enzymes. Within the core syntehsis of viral m-RNA occurs during viral DNA-RNA polymerase that is resident in the core. VIral mRNAS that are syntehsized within the core are designated immediately early mRNAS. Immediately early mRNAs are translated into immediate early proteins taht are responsible for initiating step 2 of the uncoating process.
uncaoting proteins of viral origin then cause the release of the viral DNA from the viral core structures into the cytoplasm.
Stages of vaccinia replication 3 and 4
- early events: uncoated viral (parental) is then transcribed into “early” mRNAS which are translated into early proteins.
Early proteins have eenzymatic activities which are required for viral DNA replication. (DNA dependent DNA polymerase, thymidine kinase, exonnucleases)
- DNA replication occurs in defined regions of the cytoplasm to yield progeny DNA molecules
Stages of vaccinia replication: 5 and 6
- Progeny DNA is transcribed into “late” mRNAs, which is translated into “late” proteins. Late viral proteins are mostly structural proteins. Pox viruses are unusual in that they syntehsize one layer of theri own envelope (de novo syntehsis) and acquire another layer from cell membrane.
- Progeny virus particles form and accumulate in the cytopalsm to yield infectious particles. Microtubules enable progeny virus partciles to move to the surface of cell to egress.
Disease: smallpox erradication
model for eradication of a disease with a worldwide disease
Small pox clinical transmission and stages
variola virus enter into the UR as an aerosol to initiate the infection process. Virus multiplies in the respiratory mucosa and regional lymph nodes.
A transiet viremia then develops which enable virus to spread to an replicates in cells of internal organs and bone marrow. Virus is released into the blood after this process and
2nd viremia > infection moves to cell of skin, skin rash begininng usually first on the face then spreading centrifugally (exanthem and enathem)
Exanthem
rash or lesions of skin
Enanthem
lesion of mucous membranes
small pox clinical considerations: Reason for erradication
Time period between first exposure to virus and infection of internal organs w/ overt symptoms represent a long incubation period of about 6-17 days. Long incubation period is a very consistent feature, allows enteded time for vaccination during incubation period. The sooner vaccination is begun after SPV exposures (first 4 days is best), the better the chance for blocking infection (reason for erradication)
Smallpox SX
severe fever 1-4 days prior of onset of rash, >101 F, PRODROMAL SYMPTOMS
Smallpox Rash developmented
Macule > papule > umbilicated vesicle > pustule > crust and scarring, involves all leayers of epidermis and dermis, crust are infectious which is unlike some other skin lesions caused by other viruses. (umbilicated indicates an indented top surface). most lesions develop first on face and then distal portion of extremities. SPV infection includes cells in all layers of skin. One crop of lesions per area of skin, ie lesions arise in a syncrhonous manner at each site. Lesions seen on palms of hands and soles of feet.
Reasons for erradication
long incubation period
guarnieri bodies are identifiable
spread only in mad
person to person contact but not easily transmitted: ruptured pustules are infectious after which a scab may form. Upper respiratory secretions contain virus. Contagious of all are individauls who are partially immune and who have few lesions, escape detection, yet are infected by virus. Ruptured pusutles more infective than scabs but the latter may transmit smallpox.
Small pox vaccine
first generation found stockpiled and still immnogenic. Second generation . Third generation vaccine more avirulent
Vaccine responses
Primary response: follows same lesion progression as seen in actual smallpox infection; indicates no prior immunity. 8-10 days (max response) maximum size of vesicle by ninth day
accelerated response: same lesion progression as a but faster. Indicates partial immunity. 3-7 days (max response)
c. Early or immediately rponse. hypersensitivity reaction; immunity not certain 2-3 days
vaccinia gangrenosa or vaccinia necrosum
seen in those with thymic dysfucntions
spreading lesions with necrosis of skin and muscles
show importance of t lymphocytes in controlling viral infections
patients with AIDS were given experimenal vaccinia vaccine. Since their immune system was malfunctioning vaccinia infection was disseminated causing a fatal disease.
