What's the only SS DNA virus?
What is the important Parvovirus?
Describe the proteins expressed by DNA viruses and the order they are expressed in
1) Interferons and proteins involved in immune evasion
2) Proteins that induce cell cycle progression (exception: Pox because it's in cytoplasm and Parvo because it's too small)
3) Structural proteins necessary to build new viral particles
Primary Herpes Infection
Usually the worst disease attack (if it's symptomatic); instead of a single lesion there will be multiple
Treatment for CMV
Name the naked DNA viruses
PAPP Parvovirus Adenovirus Papillomavirus Polyomavirus
Tropism for adenovirus
mucosal epithelium (primary), lymphoid, mesenchymal
Second Line Antiviral drugs
These drugs do not require phosphorylation; they carry higher toxicity to host however. They include Cidofovir and Foscarnet
Describe the stability of Enveloped vs Naked viruses
Naked viruses are more capable of persisting in the environment and are resistant to chemical inactivation - more likely to lead to epidemic outbreaks
How can HSV-1 lead to Corneal Blindness and Encephaly?
Virus is latent in Trigeminal Ganglia, so if virus goes down V1 it can reach the eye. Alternatively, if the virus goes backwards along the nerve it can reach the Temporal Lobe of brain (usually only occurs in people who get many outbreaks a year)
Describe prevalence of CMV
CMV is widely dispursed throughout the population, and the vast majority of people are infected but remain asymptomatic. Most people get it during perinatal period or during reproductive years.
Acidophilic inclusions seen in epidermis due to an accumulation of virons of Pox virus
The worse disease associated with Gamma Herpes viruses is what?
Their latency phase - Cancer
- SV 40
- JC Virus
- BK Virus
- Merkel Cell Virus
Where do JC and BK viruses remain latent?
Kidney, lymphocytes, and brain
How Alpha herpes viruses evade immune system during latency phase
They produce NO PROTEIN during latency phase; only a small intron of RNA is expressed called the LAT Transcript
Name the Alpha Herpes Viruses
HSV 1, HSV 2, VZV
Diseases associated with HSV-2
- Genital infection
- Oral infection
- Congenital Herpes in Neonate (bad)
What DNA Viruses have circular DNA?
Papilloma Polyoma Hepadna
Replication Machinery encoded by DNA viruses
1) DNA-Dependent-DNA Polymerase
2) Thymidine Kinase
Hepadna encodes Reverse Transcriptase
Why do we care about the site of viral replication?
We know that if we see intranuclear inclusions it's likely a DNA virus (exception: Pox), and if we see cytoplasmic inclusions it's likely an RNA virus (exception: Influenza and Retroviruses)
Trophism of Varicella Zoster Virus
Immune Cells and Neurons, epithelial cells, T cells
Diagnostic important of Syncytia
If multi-nucleated giant cells are present it indicates the virus is enveloped
Name the Gamma Herpes viruses
EBV, HHV 8
Drugs that target DNA-Dependent-DNA-Polymerase
Foscarnet and Cidofivir
What do Alpha and Beta Herpes viruses have in common?
Their active replication stage is associated with disease
What DNA virus has a pleomorphic/filamentous shape?
Transmission of adenovirus and incubation time
Mainly fecal-oral, also Respiratory
incubation of 5-9 days
Complications of congenital CMV
- Number one cause of viral birth defects
- Microcephaly and Hearing loss are main problems
- Periventricular calcifications
- Also Jaundice, retinitis, blueberry muffin rash, CNS damage
- Hydrops fetalis
Transmission of Parvovirus
Aerosol or Transplacental
Herpes infection that's common on the neck of wrestlers
Describe Monkey B Virus
It's an alpha herpes virus that typically infects monkeys but is asymptomatic in them. When it infects humans due to scratches or bites, it leads to early flu-like symptoms, then progresses to neurological symtoms such as paresthesia, disorentiation, dysphagia, ascending paralysis, encephomyelitis, coma, and DEATH
Do antiviral drugs work on latent viruses?
NO - they require ACTIVE viral replication
What is the significance of the extremely high prevalence rate of DNA viruses in terms of diagnosis?
Serology testing is useless; must test for viral proteins
Name the Beta Herpes Viruses
CMV, HHV 6, HHV 7
Diseases associated with HSV-1
- Cold Sores
- Ocular Infections - leading cause of ocular blindness
- HSV Temporal Lobe Encephalitis
Main difference between HSV-1 and HSV-2 inections
HSV-1 infections typically recur about once a year; HSV-2 infections recur multiple times a year
How are HSV-1 and HSV-2 diagnosed?
- HSV-1 and HSV-2 are distinguished by ELISA antibody type specific assays against Glycoprotein G (most rapid method, especially for possible encephalitis case)
- Tzank Test is the old method
Reactivation Phase of Herpes Virus
Recrudescent Disease - single cold sore (because only one neuron reactivated)
Asymptomatic Shedding - the virus is active but the patient sees no symptoms; this is how most transmission occurs
Disease caused by BK virus
Hemorrhagic Cystitis in organ transplant patients
Where does HHV-2 remain latent
Diseases caused by CMV
- Mononucleosis (adolescents)
- Severe Congenital Infections (hearing loss, periventricular calcifications, blueberry muffin rash, hydrops fetalis)
- Esophagitis with linear ulcerations
- CMV Colitis with ulcerated walls
- CMV Retinitis (CD4 Count < 50)
- CMV Pneumonia/ severe systemic infection (recent organ transplant)
Basophilic sites of DNA replication within cytoplasm of cells infected with a Pox virus
Diseases caused by HHV-6 and HHV-7
Roseola Infantum (Sixth Disease)
- Can cause febrile seizures and encephalitis
Looks for multi-nucleated giant cells (Syncytia) which indicates the virus has an envelope. This can be coupled with intranuclear/cytoplasmic inclusion tests to further narrow down which virus you might be dealing with. Most important for new viruses nowadays since we have more specific tests for current ones
Because Smallpox vaccine is a live-attenuated virus, 1:5000 may get vaccinia. This is only a problem for neonates and immunocompromised. Right now, only CDC workers and Military are at risk. The CDC has immunoglobins to treat this
Diseases caused by adenovirus
1) Acute Respiratory Disease (ARD) - seen in military recruits
3) Sporadic follicular Conjunctivitis - benign conjunctivitis and most common eye infection
4) Epidemic keratoconjunctivitis - pink eye; can spread in public pools
5) Gastroenteritis - second most common cause of infantile viral diarrhea; people can shed this virus in stool months after infection
Cancerous protein made Polyoma viruses
Large T (LgT)
Property of enveloped viruses that allows them to merge neighboring cells together to form multi-nucleated giant cells
Herpes Virus pathogenesis
- Primary Lyctic Infection occurs because virus gains access to body through mucosal breaks
- During latent infection, virus persists in ganglia (immunoprivileged)
- If a stress occurs, the virus reactivates - only ONE neuron gets activated, so you usually only get one cold sore
Describe vaccines availble for VZV
- Live-attenuated VZV vaccine given to children to prevent chicken pox
Zostavax - Live-attenuated vaccine with 10x more concentrated dose given to adults over age 60 to invoke a stronger T Cell response in order to prevent shingles/neuralgia
Tropism of Parvovirus
Epithelial cells in S Phase of cell cycle, Erythroid progenitor cells, Endothelial cells of Blood vessels
Diagnosis of JC virus/PML
Multiple non-ring-enhancing lesions in brain of immunocompromised patient
How are HHV-6 (a and b) and HHV-7 transmitted?
- HHV-6b is transmitted in saliva
- HHV-6a is transmitted sexually
- HHV-7 is transmitted in breast milk
Disease caused by JC Virus
Progressive Multifocal Leukoencephalopathy
What DNA virus lacks an icosahedral structure?
Poxvirus; it is a multi-enveloped Ovoid Block (complex)
Trophism of Herpes Simplex Virus
Neurons and epithelial cells
Where do EBV and HHV-8 (Kaposi's Sarcoma) remain latent?
Caused by BK virus; diffuse inflammation of the bladder leading to dysuria, hematuria, and hemorrhage. Associated with bone marrow transplant patients
Only Pox virus we have to worry about; usually only occurs in immunocompromised
Transmissibility of VZV
Aerosol transmission so highly contageous
What enzyme activates nucleoside derivatives in Alpha Herpes Viruses? CMV?
- Alpha Herpes Viruses: Thymadine Kinase
- CMV: Phosphotransferase
Where do HHV-6 and HHV-7 remain latent?
Trophism of Cytomealovirus
What is a potential problem with immune-modulating monoclonal antibodies?
They can lead to a reactivation of JC virus which results in Progressive Multifocal Leukoencephalopathy
Does B19 have a vaccine?
No, but most people have had it and have antibodies for it
Cancerous proteins made by papilloma viruses
E6 and E7 transforming proteins
What is unique about HHV-6?
It can be integrated chromosomally and inherited genetically
Envelope of Pox viruses
Pox viruses have two envelopes associated with one virus. Both forms are infectious. The body has to neutralize both versions of envelopes, and vaccines must target both forms
Pathogenicity of Parvovirus and special requirements
Direct cell damage by viremia as well as humoral immune response.
Must invade actively dividing cells since it does not encode proteins that encourage cell division; Alternatively it can co-infect with another DNA virus that has this machinery
What are the only Herpes viruses that do not infect a majority of the population
Kaposi's Sarcoma (HHV 8) and HSV-2
Other diseases/co-infections associated with Herpes infections
- HSV-2 is associated with HIV infection
- HSV-1 is associated with Alzheimer's
Complication of Shingles
Post Herpetic Neuralgia - extremely painful due to death of neurons. Unlike HSV, when VZV reactivates many neurons are affected and you can get a lot of neuronal death
Diagnosis of BK Nephropathy
Characteristic viral inclusions in biopsy materials; nuclear enlargement with "smudgy" or "ground glass" appearance
Where does VZV remain latent
Dorsal Root Ganglia
How to nucleoside antivirals work?
They must be phosphorylated in the cell, and this only happens in actively dividing cells. Then they have very high affinity for Viral Polymerase
Diagnosis of CMV
- Cytomegaly on histology with "owl-eyes" appearance
Monospot test if patient presents with mono; if test is negative the virus causing mono is CMV
IgM antibodies indicate primary acute infection
Pathogenicity of adenovirus
Very stable in the environment and resistant to chemical/physical agents (including chlorinated pools) as well as adverse pH. Causes direct cell damage via replication with strong cellular immune response
Periventricular Calcifications on neonate indicate what?
Congenital CMV infection
Where does HHV-1 remain latent
Where does CMV remain latent
hematopoietic progenitor cells/monocytes
Main mechanisms of viral drug resistance
- Alteration in Thymidine Kinase/Phosphotransferase (valacyclovir and famciclovir)
- Alteration in DNA Polymerase (valacyclovir, famiciclovir, acyclovir, adn foscarnet)
What do Beta and Gamma herpes viruses have in common?
Their latencey stage is in leukocytic immune cells
Usually occurs on doctors and dentists from treating patients' mouths who have an active Herpes infection without wearing gloves; they get a Herpes infection on their thumb
Diseases caused by B19
Pregnancy-associated hydrops fetalis
Aplastic anemia and Arthritis
Rash (erythema infectiosum)
1) Fifth disease (Erythema infectiosum) - "slapped cheek rash"
2) Hydrops fetalis - causes severe hypoxia in fetus due to anemia
3) Persistent infection in Immunocompromised
4) Aplastic Crisis and Relapsing Chronic Anemia in those with RBC disorders like Sickle Cell