DNA Viruses.... The Basics

Concepts:

1. All DNA viruses, except, Parvoviruses are double-stranded (ds).
2. All, except, Poxviruses duplicate their DNA in the nucleus.
1. all, except, Pox -" in - a - Box" are icosahedral
3. Naked DNA viruses are P.A.P. (You are naked to receive a "PAP")
   
1. Parvo
2. Adeno
3. Papova

Replication:

1. DNA viruses, except Hep B, duplicate their DNA by using it as a template to make DNA
1. Hep B: Enveloped ds DNA virus that makes an RNA intermediate.
   
1. All the other hepatitis viruses: All RNA virues, replicate thru RNA intermediates!
2. A Polymerase, which is very similar to the retroviral reverse transcriptase, makes the new DNA from the RNA intermediate.

Parvovirus B19:

• B19 is a naked ssDNA virus that causes fifth disease.
• Fifth disease: (erythema infectiosum, a.k.a. slapped cheek fever)
• infects adolescents, mild fever, and a recurring "slapped cheek" appearance with lacy rash on the arms and then body.
• May cause Chronic anemia in immunocompromised pts.
• aplastic crisis in sickle cell.
• Can cause hydrops fetalis

PapOvaviruses: The "O" is for circular DNA. It is also Oooh, naked.

• Two groups:
  
• Papilloma (wart) viruses
• Polyomaviruses
• Human Papillomaviruses cause warts. They are transmitted by direct contact. Will cause a +PAP smear.
• Notice how the higher the #, the worse it becomes.
  
• Plantar warts are HPV 1 and 4: both benign
• HPV 6 & 11 are the most common cause of anogenital warts (condylomata acuminata), which are sexually transmitted and laryngeal warts (usually seen in very young and sometimes aquired at birth).
• Cervical intraepithelial carcinoma is most commonly assoc. w/ HPV 16 and 18.
• The Early proteins of these oncogenic HPVs, E6 and #7, inactivate tumor suppressor fxns of p53 and p110-rb, respectively.
• Polyomaviruses:
  
• BK and JC are common but cause disease on in compromised pts.
• BK - K is for kidney disease and often ends up w/ the patient needing a kidney transplant.
• JC - assoc. w/ PML: progressive multifocal leukoencephalopathy.

ADENoviruses: Think of "a den" of coughing kids and adults w/ an ____ itis.

• Pharygoconjunctivitis and keratoconjunctivitis: non purulent pink eye. inflammed and watery.
• Acute respiratory diseases: most serious is interstitial pneumonitis in immunocompromised.
• Adenoviruses 40 and 41 cause gastroenteritis.
  

HEPaDNAvirus: Hep B is an enveloped, partially ds DNA virus.

• Transmission: The vowels are in the bowels for hepatitis, therefore, hep B is blood/parenterally or sex.
• B/c, as you remember, it replicates thru an RNA intermediate, it carries in the mature virus particle (virion) a DNA polymerase with reverse transcriptase and DNA-dependent DNA polymerase activity.
• DNA transcribed into RNA intermediate copied w/ reverse transcriptase into the new genomic partially stranded DNA
• Disease is acute or chronic
• Chronic: presence of HB_sAg > 6mo.
  
• On ave., pt is infectious for about 5 years and unable to suppress the production of HB_sAg.

• Diagnosis: made by serology, testing for the presence of IgM to HB_cAg, anti-HB_sAg, and HB_sAg.
  
• The presence of anti-HB_eAg indicates a lower risk of transmission of the virus.

HERPESVIRUSES: Large family of enveloped, icosahedral, ds DNA viruses

• Herpes simplex, varicella-zoster, cytomegalovirus, epstein-Barr,
  
• Viruses of the herpes family are the ONLY ones whose envelope is from the host cell nuclear membrane modified by viral glycoproteins!

1. HSVs. May cause acute or latent infections:
1. Latent: HSV DNA is present in the nerve ganglia, and alpha (immediate early) proteins are expressed, but the beta viral proteins such as the HSV thymidine kinase and DNA polymerase (required for new DNA synthesis and for virus production).
1. Thus, anti-HSV Rx like acyclovir (protease inh.), which inhibits DNA polymerase, do not wipe out latent infections!
2. HSV - 1 usually above the waist - gingivostomatitis, keratoconjunctivitis and meningitis
   
3. HSV - 2 usually below the waist - genital herpes and neonatal infections
2. VZV. Primary infection: varicella or chickenpox.
1. Children are considered contagious for 6 days after all lesions have dried
2. VZV vaccine is an attenuated (live, but modified) strain of the virus.
3. Secondary infetion: herpes zoster or shingles. Clusters of vesicular lesions, usually along a single sensory dermatome
4. Immunocompromised: Tx is w/ varicella zoster immunoglobulin - VZIG and oral acyclovir
5. 
3. CMV: extremely common
1. Transmission: across placenta, aquired during birth or through mother's milk or direct contact w/ others, sexual contact or blood.
2. Large cells w/ typical purple intranuclear inclusion bodies surrounded by a "halo" "owls eyes"!
3. 
4. Disease: most are asymptomatic, but may be mononucleosis-like in adults.
1. clinical dx - retinitis and interstitial pneumonitis in immunocompromised
1. severe in immunocompromised
2. cytomegalic inclusion disease - neonatal infection - hepatosplenomegaly w/ TTP, pneumonititis and CNS calcifications& microcephaly.

1. EBV -
   
1. Infects by binding CD-21 molocules on B lymphocytes
1. 15-25yo. EB infectious mononucleosis
1. SEVERE fatigue, pharyngitis/tonsillitis similar to strep, postcervical lymphadenopathy, hepatomegaly (elevated ALT) and splenomegaly.
2. Downey type II cells
   
3. Heterophile antibodies - unique to EBV infections - which react w/ animal red blood cell antigens (rather than the virus)
1. Monospot

Poxviruses - pox - Pox in a box - very large and unusual ds DNA viruses, often described as having a brick-shaped complex appearance (pox-in-a-box)

1. mAKE ALL NUCLEIC ACIDS IN THE CYTOPLASM. They require a virion-associated transcriptase.
   
2. directs synthesis of its own envelope
3. infection w/ pox produces cytoplasmic inclusion bodies.
1. Variola: virus that caused smallpox. Extinct since 1977: You should never see the typical intracytoplasmic inclusion bodies, called Guarnieri bodies, since they have "guone" away.
2. Vaccinia virus was the immunogen in the vaccine that led to the successful eradication of smallpos. Vaccinia is of uncertin origin.
3. Mulluscum contagiosum: causes benign, pincushionlike, pink tumors w/ nipplelike indentations. Virus-infected cells have large eosinophilic cytoplasmic inclusion bodies called mulluscum bodies.
1. severe in immunocompromised - of course!
2.