DNA Viruses Flashcards
What are 3 key concepts of DNA viruses
- transcription and replication in nucleus (not poxvirus)
- host RNA polymerase transcribes mRNA (not poxvirus)
- viral or host DNA polymerase replicates genome
Steps in DNA Virus replication are very similar to steps in RNA Virus replication. In DNA virus replication, transcription of mRNA is carried out by host and/or viral RNA polymerase?
In DNA virus replication, transcription of mRNA is carried out by host RNA polymerase
In DNA virus replication, replication of the genome is carried out by host and/or viral DNA polymerase?
host or viral DNA polymerase
T/F: Both cellular and viral transcription factors regulate transcription of mRNA by host RNA polymerase
True
T/F: Viral transcription factors that play a role in regulating DNA virus transcription are important virulence factors and may even be essential proteins
True
What kinds of DNA viruses use host DNA polymerase to replicate genome? What about those that use viral DNA polyermase?
The size of the DNA virus can predict whether it uses viral or host DNA polymerase. Really small DNA viruses can’t fit its own viral DNA polymerase so they will use host DNA polymerase. Larger DNA viruses will encode their own polymerase and accessory proteins.
Herpesviruses use viral or host DNA polymerase to replicate genome?
viral DNA polymerase to replicate genome because herpesviruses are big DNA viruses that are capable of encoding their own polymerase and accessory proteins
Adenovirus use viral or host DNA polymerase to replicate genome?
viral DNA polymerase to replicate genome because adenoviruses are big DNA viruses that are capable of encoding their own polymerase and accessory proteins
T/F: DNA viruses are as diverse as RNA viruses (undergo as many mutations)
False because DNA viruses are more stable than RNA viruses since DNA viruses polymerases have high fidelity and proofreading capabilities and are genetically more stable. Recombination still occurs between and within genomes and mutations, but just not as many as RNA viruses
Which 3 DNA viruses are the most common cause of disease?
- adenovirus
- papillomavirus
- herpesvirus
Adenovirus Disease affects the respiratory tract. What are some symptoms? Can it cause problems in extrapulmonary sites as well?
Adenovirus disease can cause a bad cold with a fever, pharyngoconjunctival fever, laryngitis and cough, and pneumonia. It can also cause gastroenteritis, epidermic keratoconjunctivitis, and acute hemorrhagic cystitis.
Transmission of Adenovirus Disease
-aerosol, fecal-oral, objects, poorly chlorinated swimming pools
Who are most susceptible to adenovirus disease?
children and military recruits
Explain the attachment, entry, and uncoating of adenovirus
- adenovirus fiber protein binds to cell receptor
- entry is by endocytosis
- endosome acidification causes fibers to lyse the vesicle
- capsid traffics to nucleus and DNA genome uncoats thru the nuclear pore
The adenovirus dsDNA genome is replicated in ________ by host or viral DNA polymerase?
The adenovirus dsDNA genome is replicated in nucleus by viral DNA polymerase.
Host or viral RNA polymerase transcribes adenovrius genome into mRNA?
host RNA polymerase II makes mRNA
There are 3 gene expression phases associated with adenovirus
- Immediate early (makes the polymerases and accessory proteins)
- Early
- Late (make capsid proteins)
Where does capsid assembly occur in adenovirus?
in nucleus
How do adenovirus virions egress from cell?
cell lysis
What are some tests to diagnose adenovirus disease?
- culture
- antigen detection
- PCR
- serology
Cidofovir
It’s a anti-viral drug (nucleoside analog of cytosine) to treat immunocompromised patients with adenovirus disease. It’s reserved for the most dire cases because it’s nephrotoxic
Is there a vaccine against adenovirus?
yes, but only in the military
Human papilloma virus diseases can cause epithelial diseases, such as
- common warts
- plantar warts
- genital warts
Human papilloma virus diseases can cause malignancies, such as
- head and neck cancer
- cervical cancer
- penile cancer
HPV tissue tropism
differentiated epithelial cells
State genome, shape, and whether it’s enveloped or not: Human Papilloma Virus
- ds circular DNA
- icosahedral
- naked
State genome, shape, and whether it’s enveloped or not: adenovirus
- dsDNA
- icosahedral
- naked
host or viral RNA pol transcribes HPV genome?
Host RNA polymerase transcribes dsDNA
host or viral DNA pol replicates HPV genome?
Host DNA polymerase replicates HPV genome
In HPV, list the 2 viral factors that are oncogenes
E6 and E7
How to treat warts?
- cryotherapy (freezing)
- chemical ablation (salicyclic acid, etc)
- colposcopy (minor surgery of the cervix)
List the 2 HPV vaccines and what strains they protect against and both of these viruses are VLPs. What are VLPs?
- gardasil against types 6, 11, 16, 18
- cervarix against types 16, 18
- VLPs = Virus-like particles composed of empty capsids
The initial phase of HPV infection occurs in which cell type?
basal epithelium
There are 8 different species of human herpesviruses. Infection is life-long. State the genome, structure and whether it’s enveloped or not.
Herpesviruses are big DNA viruses.
- dsDNA
- icosahedral
- enveloped
In herpesvirus life cycle, are there phases in viral gene expression?
Viral gene expression occurs in immediate early, early, and late phases
How does herpesvirus leave the host cell/egress?
by exocytosis
Define Herpesvirus latency
The genome is present in a cell but infectious virions are absent
T/F: Herpesviruses establish latency in a variety of cell types before symptoms or virus replication are apparent
True
HSV-1 Disease spread by
close contact with active lesions or asymptomatic shedding
HSV-1 Disease establishes latency in
neurons
Lesions of primary HSV-1 are found usually
above the waist (mouth, face, nose, eyes), can be genital
What symptoms may precede recurrent HSV-1 disease?
Tingling and itching may precede outbreak
Recurrent HSV-1 disease can cause contagious lesions on
lips or inside mouth, eyes, genitals, fingers
HSV-1 primary infections can cause what in the brain
meningitis (stiff neck and headache)
Recurrent HSV infections occasionally cause what in the brain
encephalitis (fever, neurologic symptoms)
What lobe of the brain does HSV target?
temporal lobe
HSV-2 Disease is spread by
close contact between mucous membranes (genital and/or oral)
Symptoms of HSV-2 are usually but not always below the waist
many lesions, pain, itching, fever, malaise, headache
Where does HSV-2 establish latency?
in neurons
T/F: Double infections with HSV-1 and HSV-2 are uncommon
False; double infections are common
What symptoms precede recurrent HSV-2 disease?
itching, tingling at lesion site a day before outbreak
HSV-2 lesions are contagious and are found on
labia, penis, anus, mouth, eyes
T/F: HSV-2 can be shed and transmitted even without symptoms
True
What diagnostic test can differentiate between HSV-1 and HSV-2?
Serology or PCR
Should people with frequent outbreaks of HSV-2 take antiviral prophylasix? Which drug?
Yes. Chemoprophylasix such as Valtrex and Famvir can be used daily to prevent outbreaks
Acyclovir
an anti-viral drug used to treat HSV
Are there vaccines against HSV-1 or HSV-2 infections?
No
Another species of herpesvirus is the varicella zoster virus, which causes chicken pox. How is it transmitted?
it’s highly contagious and transmitted via aerosol droplets
Where does varicella virus establish latency?
dorsal root ganglia
How can you tell if someone has chicken pox/varicella infection?
distinctive rash like “dew drops on rose petals”
What are some complications of Chicken pox? List 4
hepatitis, encephalitis, pneumonitis, bacterial infection of lesions (MRSA, strep)
Varicella zoster virus recurs more commonly in the elderly and immunocompromised known as shingles. List the 3 prodrome symptoms
- burning
- itching
- tingling
Shingles outbreak is diagnostic of itself because
outbreak occurs along a single dermatome
Shingle lesions are painful and itchy. Can they spread varicella to children?
Yes.
What are 3 complications of shingles?
- Bell’s Palsy
- Postherpetic neuralgia
- Retinitis
What is herpes zoster ophthalmicus?
zoster in the eye, which can destroy retina leading to blindness. Approximately 30% of zoster outbreaks affect the face.
T/F: Zoster treatment is only effective during first 3 days of outbreak
True
T/F: Acyclovir is effective anti-viral drug for zoster infection
No, only marginally effective
Foscarnet
second-line anti-viral drug against zoster
What are the two vaccines against varicella zoster virus?
Both are live attenuated virus
- Varivax prevents varicella from ages 1-50
- Zostavax prevents zoster from ages 50+
Another species of herpesvirus is Epstein Barr Virus Disease. How is it transmitted?
Transmission by saliva
What cells does epstein barr virus infect?
oral epithelial cells and B cells in tonsils
Epstein barr virus develops latency in
B cells
T/F: Childhood infections with epstein barr virus are often asymptomatic
True
Epstein barr virus recurrence is most likely due to
immunosuppression
EBV recurrences can lead to malignancies, such as
- Hodgkin Lymphoma
- AIDS-associated non-Hodgkin Lymphoma
- Post-transplant lymphoproliferative disease
- Burkitt lymphoma
- nasopharyngeal carcinoma
Blood smear of someone with infectious mononucleosis caused by epstein barr virus will reveal
elevated WBCs and atypical lymphocytosis
What are some anti-viral drugs used in treatment of epstein barr virus infection?
NONE
How to prevent infection with EBV?
NONE
Another herpesvirus is cytomegalovirus. Cytomegalovirus can cause syndrome like infectious mononucleosis. How to differentiate between cytolomegalovirus infection and epstein barr virus infection?
In epstein barr virus infection, infectious mononucleosis will present with sore throat, but in cytomegalovirus infection, the patient will not have sore throat.
Primary CMV infections are usually asymptomatic. About 50-95% of people are infected by adulthood. Why is it impt to know if pregnant women are infected with cytolomegalovirus?
CMV can be transmitted to fetus and cause congenital CMV disease. Some will remain normal, but 15% will develop late disabilities while 10% will have severe neurologic complications.
AIDS patients with CMV experience a lot of complications
CMV retinitis, gastroenteritis, pneumonitis, encephalitis. CMV causes tremendous morbidity and mortality.
Why are transplant recipients and donor routinely tested for CMV?
b/c CMV disease is a frequent cause of transplant failure and patient mortality
What’s the standard of care for transplant patients and donors in relation to CMV disease?
pre-emptive screening and prophylactic antiviral therapy
What are the 3 anti-viral drugs used in CMV disease?
Ganciclovir
Foscarnet
Cidofovir
Are there any vaccines against CMV?
No
Human herpes virus 6b and 7 (HHV6b and HHV7) infect what cells?
CD4+ T cells
Human herpes virus 6b and 7 (HHV6b and HHV7) establish latency in what cells?
CD4+ T cells
HHV6b and HHV7 are transmitted in
saliva
HHV6b and HHV7 cause Roseola infantum aka exanthem subitum. What are the symptoms?
3-day illness of high fever, followed by a faint rash on the trunk
HHV6b and HHV7 affect which age group? Any seasonality?
age 7-13 months; no seasonality
It is important to rule out _______ when diagnosing for Roseola
drug allergy
If parents insist that you give their infants with roseola abx, what should you do?
give supportive care for fever, but try to avoid giving antibiotics.
If your child’s daycare does not want your child with rosela to attend in fear of giving it to other children, what can you say?
That roseola is not contagious
List the different herpesviruses that we talked about in class
Herpesviruses are enveloped icosahedral dsDNA
- HSV-1 (HHV1)
- HSV-2 (HHV2)
- Epstein Barr virus (HHV4)
- Varicella zoster virus (HHV3)
- cytomegalovirus (HHV5)
- HHV-6
- HHV-7
- HHV-8 (not tested on)
T/F: both HPV and EBV can lead to malignancies
True; HPV can cause cervical, head and neck and penile cancer And EBV reinfection can lead to lymphoma and other malignancies
What is unique about poxvirus in comparison to the other DNA viruses?
Poxvirus is a complex dsDNA that is enveloped. It is huge and will carry its own DNA polymerase. Unlike other DNA viruses, poxvirus will replicate and transcribe in cytoplasm and poxvirus carries its own RNA polymerase
Episomes
After infecting basal lamina, HPV doesn’t really replicate and maintains as episomes, which will differenitate into keratinocytes, and undergo hyperplasia once it senses that it’s close to skin surface
symptomatic HSV-1 and HSV-2 can be treated with which anti-viral drug?
acyclovir (a nucleoside analog of guanosine) that inhibits viral TK