DNA Viruses Flashcards
What is the only family of DNA viruses that is not icosahedral?
Pox viruses
What is the genomic composition of herpes virus?
enveloped dsDNA linear; it circularizes during latency and replication
lytic type
**All herpes viruses establish a latent infection and reactivate under various conditions
what 3 families of DNA viruses have envelopes?
Pox, hepadnavirus, and herpesvirus
What is the genomic composition of hepadnaviruses?
partial dsDNA: nicked circle formation with positive strand only in regions of overlap
Where do DNA viruses replicate? What is the one exception?
In the nucleus; exception - poxvirus
What 3 strategies do DNA viruses use to maximize their genome?
Multiple promoters
Alternative splicing
Code from both strands (exception: papilloma codes from only one strand)
What is the hallmark of DNA viruses?
Distinct replication phases and reproducible patterns of expression for viral genes and viral DNA syntheses - not chaotic
4 justifications for synchronized replication phases
Prepare host environment
Diminish competition of low expression viral genes (regulatory factors) with high expression genes (structural proteins)
Avoid premature cytopathic effects
Help avoid immune detection
What gene are expressed in immediate early expression?
Regulatory proteins for replication (transcription factors, transactivators)
- do not require any new protein synthesis for expression
- use transcription factors carried in parental virion or host factors
What genes are expressed in early gene expression?
Regulatory proteins that actually participate in viral replication (think enzymes: helicase, DNA polymerase etc.)
-targets for antiviral therapy
What genes are expressed in late gene expression? What is notable about this stage?
Structural proteins for assemblying mature virions
Both parental and progeny DNA is used as template bc so much protein needs to be made: structural, not enzymatic
Not expressed until after initiation of viral DNA synthesis
Requires a shift: downregulate early gene expression except for DNA synthesis
When cytopathic effects (like inclusion bodies and syncytia) occur
Name the 2 versions of viral DNA synthesis with examples.
Host DNA polymerase mediated: replication uses host cell polymerases (Papilloma, Parvo)
Viral polymerase mediated: virus encodes its own polymerases and can inhibit action of host polymerases (Adeno, Herpes, Pox)
What are 2 draw backs to host DNA polymerase-mediated replication?
Host cell must be in S phase (dividing cells)
-some viruses encode proteins that induce cell to enter dividing state
Some viral proteins neutralize tumor suppressor factors so cause a transforming infection –> promotes cell proliferation but can also be oncogenic
What is a transforming infection?
Infection where cell proliferation is induced by turning off tumor suppressors and up-regulating growth factors, thereby leading to cancer
Name the 4 viral synthesis mechanisms with examples
1) Self priming (parvo)
2) Bi-directional (papovavirus)
3) Strand displacement (adenoviruses)
4) Rolling Circle (Herpes Virus)
What do self-priming viruses require?
an inverted terminal repetition (ITR) for 3’ OH hairpin formation
What does rolling circle replication require?
3’ OH nick and viral primases (RNA primers)
What is significant about inclusion bodies?
Site of viral DNA synthesis and virus packaging
Describe acute infection
Viruses infect, rapidly replicate and are cleared by the host
High yield of virus
Host cell is completely permissive of infection
Usually result in dramatic CPE and cell lysis
Time scale of days
Ex: adenovirus
Describe persistent infection
Infection is not cleared efficiently by the adaptive immune response –> continuous or intermitten virus production
Virus remains in primary target organ or distal site
Time scale of months - lifetime
Describe chronic infection
Type of persistent: continuous production of low/moderate levels of virus
Ex: Hep B, HIV
Describe Latent Infection
Type of persistent: viral genome is maintianed in host with little or no viral gen expression
**No virus produced during latent stage
Ex: herpes
Describe slow infection
Type of persistent: long incubation period with low/undetectable virus
ex: polyoma JC
What is viral reactivation?
When latent virus is induced to begin lytic replication
What is the infection course of herpes simplex virus?
1) infection of epithelial cells and release of progeny
2) Infection of sensory ganglion
3) Gene expression repressed; genome maintained in nucleus of neuron
4) Reactivation of latent viral genome by stress –> production of new virus
5) Spread back to mucosal surface and re-infect epithelial cells
**sometimes herpes spreads to CNS: lethal
Describe abortive infection
Virus infects cells, may express some genes but fails to produce progeny virus
CPE and transformation of host cell can still occur
NOT the same as asymptomatic infection
2 basic stages from normal cell to malignant cancer
1) Immortalization: can be achieved by viral transformation
2) Additional changes that make immortal cells malignant
Describe basic features of Parvovirus family and give examples
Linear ssDNA; naked
-insufficient DNA so requires helper virus or rapidly dividing cells
Ex: Dependovirus most co-infect with adenovirus - doesn’t cause disease (useful mode of drug admin?)
Parvo B19 requires dividing cells; causes erythema infectiosum, aplastic anemia and fetal loss
Describe basic features of Papovavirus family and give examples
circular dsDNA, naked, icosahedral
Can persist in integrated (polyoma) or episomal form (papilloma)
Release by lysis
Only human hosts
Papilloma restricted to differentiatign cels
Multiple splicing events and promoters
EX: HPV: causes cervical cancer and warts; most common STD in US (20M)
What 3 types of HPV cause cervical cancer?
16, 18, 31
What types of HPV are prevented by the vaccine?
6, 11, 16, and 18
Describe the 4 stages of papilloma infection
1) Abrasion allows virus to infect basal epithelial cells (skin precursor)
2) Amplification of episomal DNA
3) Maintenance replication in differentiating cells
4) Productive viral replication ONLY in differentiated cells
3 examples of polyoma viruses and their associated diseases
MCV: merkel cell sarcoma
BK: renal disease and hemorrhagic cysts
JCV: progressive multifocal leukoencephalopathy
Describe basic features of Adenovirus family and give examples
linear dsDNA; naked
transmitted via respiratory or ocular droplets
Causes respiratory disease, conjunctivitis, hemorrhagic cysts
Can be used as viral vecto for gene therapy
HSV 1& 2 (HCV 1&2)
Cold sores, genital herpes and encephalitis
HHV3
Varicella Zoster - chicken pox, shingles
HHV 4
Epstein barr - mono, nasopharyngeal carcinoma, Burkitt’s lymphoma
HHV5
CMV - birthd defects, retinitis, reactivation in immunosuppressed individuals
HHV6
Roseola infantum - high fever and rash
HHV8
Kaposi’s sarcoma associated
Body cavity based lymphoma (primary effusion lymphoma)
Multicentric Castleman’s disease
What makes acyclovir safe for treatment of HSV 1 and 2 and HHV3?
It’s a prodrug that requires metabolism by viral thymidine kinase to be active
Acts as guanine nucleotide analog that terminates DNA synthesis due to lack of 3’OH
Describe basic features of Hepadnaviruses including examples
Mixed ss and ds DNA; enveloped
Complex replication cycle includes reverse transcriptase step (retroid)
Tropism restricted to liver cells
Blood-blood or sexual transmission
occupation risk of health care workers
incubates for ~90 days
Can be cleared or persistent infection –> cirrhosis, primary hepatocellular carcinoma
effective vaccine available
Describe basic features of the pox virus
Largest genome of any human virus
Enveloped, linear dsDNA
Replicates in the cytoplasm: encodes everythign it needs
Ex: variola and vaccinia
