Virology Lec

• DNA viruses


  Single or double stranded, circular or linear

  
• Replication of Nucleic Acid; DNA

  1. Early transcription (dsDNA is needed, ss → ds)

  2. Early translation (mRNA → enzymes for viral DNA replication)

  3. Late transcription (dsDNA used)

  4. Late translation (mRNA → proteins for capsid)
• Viruses, many of them, do not follow strictly the central dogma process. The genome of the virus is very small and also uses and hijacks the host cell's genome to create proteins (e.g., replicase, reverse transcriptase, etc.) required for its own replication.

  
• Viral replication


  Transcription to mRNA first then translation to replication proteins, then the viral replication begins, transcription to mRNA, and translation to viral proteins (capsid proteins, etc.)
• Parvoviruses


  • Icosahedral, 18 - 26 nm diameter, single-stranded DNA, non-enveloped, 2-5 proteins, resistant to inactivations (hard to treat)

  
• Subfamilies of Parvoviridae


  • Densovirinae – contains viruses of invertebrates, requires helper viruses for productive infection
  • Parvovirinae - contains viruses of vertebrates

  
• Genera of Parvovirinae


  • Erythroparvovirus
  • Bocaparvovirus
  • Protoparvovirus
  • Dependoparvovirus

  
• Human Parvovirus B19


  First discovered in 1975, predominant parvovirus pathogen in humans (most common), only infects humans, red blood cells / progenitor cells

  
• Genotypes of Human Parvovirus B19


  • Genotype 1: quite common on west hemisphere
  • Genotypes 2 and 3: common in Africa

  
• Transmission of Human Parvovirus B19

  Respiratory aerosol/droplets (main mode of transmission), mother to child (placenta), blood products (heat and solvent resistant)

  
• Massive productive replication in erythroid progenitor cells, very high viral load (number of virus present in the body) in acute infection prior to a detectable immune response

  
• Parvovirus b19 needs p-antigen and s-phase (dna replicated), ligand = Non-structural protein 1, toxic to human cell, erythropoiesis breaks down, low production of new RBCs

  
• K9 Parvovirus has a 90% mortality rate for unvaccinated dogs
• Feline Parvovirus also has a high mortality rate
• Adenoviruses


  • Icosahedral, 70-90 nm, dsDNA, non-enveloped, many vertebrates are host

  
• Genera of Adenoviridae


  • Atadenovirus
  • Aviadenovirus
  • Ichtadenovirus
  • Siadenovirus
  • Testadenovirus
  • Mastadenovirus

  
• Human adenovirus


  Currently 88 viruses that infects humans, grouped into 7 groups, A–G

  
• Human adenovirus 1-7


  More infectious to humans, infects epithelial cells
• Adenovirus outbreaks are common, spreads easily, thus easy to catch, common in daycare, military barracks
• Herpesviruses


  • Icosahedral, 150-200 nm, double-stranded DNA, enveloped

  
• Subfamilies of Herpesviridae


  • Alphaherpesvirinae
  • Gammaherpesvirinae
  • Betaherpesvirinae
• Genera of Alphaherpesvirinae


  • Simplexvirus (HSV 1 and 2)
  • Varicellovirus (Varicella Zoster Virus)

  
• Genera of Gammaherpesvirinae


  • Lymphocryptovirus (EBV)
  • Rhadinovirus (KSHV)
• Genera of Betaherpesvirinae


  • Cytomegalovirus (Human Cytomegalovirus)
  • Roseolovirus (HHV 6 and 7)
• HSV-1 (oral herpes)


  Transmitted primarily through contact with infected oral secretions, above the waist
• HSV-2 (genital herpes)


  Acquired primarily through contact with infected genital secretions, sexually transmitted, below the waist
• Primary infection of Herpes Simplex Virus


  HSV is transmitted by contact of a susceptible person with an individual excreting virus, the virus must encounter mucosal surfaces or broken skin for an infection to be initiated, it can travel to our nervous system which can now start the latent cycle

  
• Globally, 67% of the population is infected with herpes (HSV1), genital herpes (HSV2) around 10%
• Latent infection of Herpes Simplex Virus


  Virus resides in latently infected ganglia in a nonreplicating state, only a very few viral genes are expressed, viral persistence in latently infected ganglia lasts for the lifetime of the host

  
• Recurrence of Herpes Simplex Virus


  Provocative stimuli can reactivate virus from latent state, the virus transits via axons back to the peripheral site, and replication proceeds at the skin or mucous membranes, stress can trigger recurrence but not all herpes latent infections will recur

  
• Genital herpes


  • Usually caused by HSV-2
  • Primary infection can be severe
  • Generally lasts 3 weeks
  • Characterized by painful lesions on the genitals
  • Less severe for people with HSV-1 immunity
  • Like oral herpes, genital herpes also does not always recur
• Herpes ulceration of the vulva and penile

  Penile herpes simplex (HSV-2) infection
• HSV Keratoconjunctivitis


  • Rare compared to HSV 1 and 2
  • Recurrent lesions of the eye are common and appear as dendritic keratitis or corneal ulcers or as vesicles on the eyelids
  • With recurrent keratitis, there may be progressive involvement of the corneal stroma, with permanent opacification and blindness
  • Dye is used to detect lesions
  • Common symptoms = blurry vision and blindness

  
• Skin Infections


  • Herpetic whitlow (rare for healthy people, usually seen in fingers)
  • Herpes gladiatorum (common for wrestlers)
  • Burn injuries (exposed skin can lead to attachment of the virus)
  • Atopic dermatitis (eczema) HSV infection of other areas
• HSV spreading to the CNS

  • Causing meningitis (inflammation of meninges outer covering of the brain) and encephalitis
  • Typically in the temporal lobe
  • Commonly happens during reactivation as a virus escapes into the bloodstream

  
• Neonatal HSV


  • Transmission happens at birth
  • Neonatal HSV may appear as: Disseminated multiorgan disease (occurring in about 25% of neonates with infection), Localized CNS disease (about 35%), Localized infection of skin, eyes mouth about 40%
  • If not treated, this can cause organ failure, sepsis, etc.

  
• Transmission of HSV


  • Can spread by asymptomatic shedding
  • Most contagious when virus-filled lesions are present
  • Herpes virus can be in saliva and genital secretions, even without lesions

  
• Diagnosis of Herpes


  • How skin or mucous membrane lesions look
  • Confirmation: Look for viral DNA with PCR, Antibody response to virus, Growing virus in culture

  
• Treatment


  • Often resolves without treatment
  • Antiviral drugs: Acyclovir, Famciclovir, Valacyclovir (reduce pain and speed healing, best if taken at start of prodrome)
• Varicella Zoster Virus


  • Causes 2 diseases: Varicella (chickenpox) - primary infections, Herpes zoster (Shingles) - reactivation of varicella
  • Same subfamily as HSV1 and 2