Dna Viruses

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Big picture chart of DNA Viruses:

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-All DNA viruses are eicosahedral!
-Herpes is enveloped.

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Herpesviridae- key points
-structure

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-Herpesviridae
-Key points:
*Large and complex
*All have similar viral structure
-Enveloped
-Icosahedral capsid
-Linear, double-stranded DNA genome
*Viral replication & assembly occurs in the nucleus
*All can establish LATENCY with their hosts.

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3 subfamilies of herpesvirus?

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-alphaherpesvirus
-betaherpesvirus
-gammaherpesvirus

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What is cytomegalovirus and when can it be dangerous?

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-A Betaherpesvirus
-Dangerous in the immunocompromised (HIV-infected are prone to this)

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Hallmark of all herpesviruses?

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-Latency
-Hallmark of all herpesviruses!!!!
-Quiescent (non-replicating) state from which virus can be subsequently reactivated.

-Mechanisms and site of latency, the frequency of reactivation, and type of recurrent disease is unique to each herpesvirus

*cold sores
*shingles rash following dermatome

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How does the site of initial infection compare to the site of latency in herpes viruses?

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-They're in different locations.
-Latency often in nerve ganglia, leukocytes.

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DNA Virus Replication key points:

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-Replicate in the nucleus
-Regulation of transcription is under “cascade control”

1. Immediate early proteins (a): important in the regulation of virus gene transcription; viral protein synthesis not required.

2. Early proteins (ß): additional transcription factors and enzymes involved in replication of viral DNA.

3. Late proteins (g): mainly structural proteins.

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-Tzanck smear is used to show presence of multinucleate giant cells.
-HERPES viruses

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Poxviridae:
key points-
what's unique about it?

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-Large, genetically complex DNA viruses with oval to brick-shaped morphology.
*Multiplies entirely in the CYTOPLASM.
-Include the human viruses variola (smallpox) and molluscum contagiosum (STI), as well as some viruses that naturally infect animals but can cause incidental infection in humans (zoonosis).
-Eosinophilic inclusions in cytoplasm of epithelial cells.

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-Structure of the vaccinia virus (a pox virus).
-Within the virion, the core assumes the shape of a DUMBBELL because of the large lateral bodies.
-Virions have a double membrane; the "outer membrane" assembles around the core in the cytoplasm, and the envelope is acquired on exit from the cell.

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Pathogenesis of Pox viruses:

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-1˚ and 2˚ viremia.

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-Lesions in pox all look the SAME.

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top left: Molluscum contagiosum. Skin lesion.

bottom left: Epidermis is filled with molluscum bodies (eosinophilic cytoplasmic inclusions).

bottom right: Orf lesion on the finger of a taxidermist.

-These are all POX viruses.

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Adenoviridae KEY POINTS:

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-Key Points:
*>100 serotypes identified; 49 infect humans.
*Serotype is mainly a result of differences in the penton base and fiber protein, which determine the nature of tissue tropism and disease.
*Among the most common causes of viral disease
-Respiratory tract infections (Ad 4 and 7)
-Ocular infections (Ad 3 and 7)
-Urinary tract infections (Ad 11 and 21)
-Gastrointestinal infections (Ad 40 and 41; lack of envelope helps it survive low pH)
*Viruses cause lytic and latent infections.

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-structure of an adenovirus
-∆ in the "spikes" determines the target for entry.
-especially cause pediatric respiratory infections.

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Most common serotypes of Adenovirus?

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1-7; these are most important.

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MECHANISMS OF ADENOVIRUS SPREAD:

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-usually self-limiting
-if individual is immune-compromised, there's a chance of spread into skin and other organs.

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-Adenovirus!
-Ocular: conjunctivitis “pink eye”; swimming pool conjunctivitis
-virus can survive swimming pool chemicals

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Key points about this virus type:

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-Papovaviridae

-Key Points:
-Small icosahedral capsid virion
-Supercoiled, double-stranded circular DNA genome.
-They can induce both lytic infections, and either benign or malignant tumors, depending on the infected cell type.
-Love to atk basal epithelial cells.

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PAPOVAVIRUS SUBFAMILIES:
-and important virus traits for specific viruses

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*JC and BK are usually asymptomatic, UNLESS someone is immunocompromised.
-BK- renal problems
-JC- causes PML
-Over 100 serotypes of HPV!

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Summary of traits of Papilloma and Polyoma viruses:

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-HPV 16, 18 can cause cervical cancer.
-HPV 6, 11 also cause genital warts.

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Papillomavirus Genome and important traits:

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-8 kilobase genome.
-circular
-L1 and L2 are late genes; code for capsid.

-Sometimes, it can insert itself into host genome between E1 and E2. [halts viral replication]
-E6 and E7 can disrupt normal cell cycle in host; interfere with p53 and Rb --> cancer! [doesn't halt E6/E7 PRO production]

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Papillomaviruses- Encounter and Pathogenesis

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-Acquired by direct contact and infects epithelial cells of skin and mucous membranes. CAN BE CASUAL--EVEN A HANDSHAKE.
-Virus persists in BASAL layer and then produces virus in terminally differentiated keratinocytes.
-Tissue tropism and disease presentation depend on papillomavirus type.
-Can cause benign outgrowth of cells into warts.
-Certain types are associated with dysplasia and may become cancerous with the action of cofactors.
-DNA can become integrated in the tumor cell chromosome.

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PROGRESSION OF HUMAN PAPILLOMAVIRUS INFECTION:

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PAPILLOMAVIRUS PATHOGENESIS:

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-1˚ infection of basal layer cells.
-Uses cofactors in basal layer to proliferate.
-E7 ensures basal cells proliferate.
-E6 ensures proliferating cells don't undergo apoptosis.
-This is how warts grow.

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CLINICAL SIGNIFICANCE of HPVs:

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-HPVs cause diseases that cover the spectrum from simple warts to malignancies.

-Warts can occur on any part of the body, including cutaneous and mucosal surfaces.

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Examples of cutaneous HPV warts:

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Cutaneous Warts:
a. common (fingers, hands)
b. plantar (sole of foot)
c. flat (arms, face, knee)

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Examples of mucosal HPV warts:
-which HPV strains are they cause by?

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a. anogenital warts (condyloma acuminata)
- 90% caused by HPV-6 and HPV-11
- can become quite large but lesions are usually benign and regress spontaneously.
b. Cervical neoplasia and cancer
- associated with infection of female genital tract by HPV 16, 18, 31, and 45.

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Cutaneous warts from HPV.

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-Mucosal warts from HPV.

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Parvovirus Key points:

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-Smallest of the DNA viruses.
*B19: only member known to cause human disease
*Requires rapidly dividing cells in order to replicate.
*Causes fifth disease

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1. Regarding adenoviruses, which one of the following statements is most accurate?
 
A. Acyclovir is the drug of choice for life-threatening infections.
B. They cause pharyngitis, pneumonia, and conjunctivitis (“pink eye”).
C. The adenovirus vaccine is recommended for all children prior to entering first grade.
D. Laboratory diagnosis depends on seeing multinucleated giant cells on biopsy.

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B. They cause pharyngitis, pneumonia, and conjunctivitis (“pink eye”).

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2. The purified genome of certain viruses can enter a cell and elicit the production of progeny viruses (i.e. the genome is infectious). Regarding these viruses, which one of the following statements is most accurate?
 
A. Their genome RNA has positive polarity.
B. Their genome RNA is a double-stranded.
C. They have a polymerase in the virion.
D. They have a segmented genome.
E. They require tegument proteins in order to be infectious.

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A. Their genome RNA has positive polarity.
*prototype is polio virus.

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3. Many viruses are highly specific regarding the type of cells they infect. Of the following, which one is the most important determinant of this specificity?
 
A. The polymerase in the virion.
B. The viral mRNA
C. The surface glycoprotein
D. The inner matrix protein

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C. The surface glycoprotein

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5 most common childhood viral infections?

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*(Varicella, rubella, roseola, measles, fifth disease!)