Prions and DNA Viruses Flashcards
What is the tertiary structure of prion proteins? What is the diseased structure? Which human chromosome is the gene for this protein located?
Normal is alpha-helical, diseased is beta sheets that aggregates into amyloid rods (fibers) Chromosome 20
What type of disease is caused by prions? How does it present?
slow neurodegenerative disease *functional disorder of the cerebellum *loss of muscle coordination (ataxia, difficulty walking) *dementia and diminished intellect, progressive insomnia
What percent of Creutzfeldt-Jakob Disease are Idiopathic in nature? Genetic (examples)? Acquired (examples)?
idiopathic: 90% - (~68yrs) genetic: 10% - Gerstmann-Straussler-Scheinker syndrome (GSS) and Fatal Familial Insomnia Acquired: small percent - Kuru and vCJD (~28yrs)
What are the 4 ways to diagnose prion disease?
- Brain MRI shows amyloid in cerebellum 2. Prion accumulate in tonsils of patients 3. Elevated levels 14-3-3 or tau protein in CSF 4. Proteinase k resistant PrP^Sc in tonsil biopsy by Western blot
- childhood viral infection
- spread late winter/spring
- resp droplets/oral secretions
- mother to fetus during pregnancy
- 65% adults serotype positive by 40yrs
- erythema infectiosum
- blotchy/raised red rash and polyarthritis
- naked DNA
B19 Virus– Parvovirus common name: 5ths disease
What can be the result of an in-utero B19 infection of a fetus?
fluid retention -> edema; edema in a fetus = hydrops fetalis
stillbirth
anemia
What is the name for slapped-cheek syndrome? What virus is commonly responsible for this presentation?
erythema infectiosum– B19, Parvovirus
B19 Epidemiology/Pathogenesis
*nasopharynx–> bone marrow
*target erythroid precursor cells that possess P antigens
*pathology from cytolysis (anemia) and immune response (rash & arthralgia)
*Mild prodrome- no symptoms to fever, sore throat, low HB
Name the virus responsible for this characteristic rash. Besides the rash, what are the other forms of diagnosis?
B19, Parvovirus
Serology for B19 IgM/IgG, PCR for viral genome
- Naked DNA
- causes lytic, chronic, latent and transforming infections
- most prevalent STI, transmitted also from fomites
- warts from virus induced cell growth in basal layers (1-6 months)a
- Slight cervical itching with soft, flat, raised cauliflower shaped warts
- CD8 T may cause wart to regress
Human Papillomavirus (HPV)
HPV Epidemiolgy
- ~20 million infected in USA (6 million new cases each year)
- induces epithelial proliferation (inhibit p53, p105RB)
- Warts from virus induced cell growth in basal layers
- Warts apear 1-6 mo, sooner in IC people
- CD8 T cells (CMI) cause warts to regress
Name the virus responsible for this skin presentatation. What is the name of theses structures? What are the other tests that can be performed to confirm this diagnosis?
HPV, warts
benign self-limited (dome shaped, flat) proliferation (on skin or mucous membranes)
DNA probes and PCR
Regular Pap tests for women - presence of koilocyte (enlarged keratinocytes with clear halos)
Which HPV strains are responsible for ~90% anogenital warts?
Which HPV strains are responsible for head/neck tumors? Why are these dangerous in young children?
Which HPV Strains are responsible for ~70% cervical cancers?
HPV-6/-11 (for both warts and head/neck tumors)
tumors may be serious in children infected at birth since it could obstruct airway
HPV-16/-18 for cervical cancer
- naked DNA
- immunocompromised individuals
- latent inection kidneys
- severe urinary tract infection (hemorrhagic cystitis)
- common in hematopoietic stem cell transpalnt recipients
- seen in patients 6 mo after receiving renal allografts
Polyomavirus BKV
- naked DNA
- immunocompromised individuals
- latent infection of kidney, B-cell, monocyte-lineage cells
- swollen oligodendrocytes (demyelination) w/ nuclear inclusions
- Progressive multifocal leukoencephalopathy (PML)
- Multiple foci of demyelination, usually cerebral hemisphere
- neurologic symptoms - speech, vision, muscle coordination
- followed by paralysis of the arms and legs and finally death
Polyomavirus JCV
Polyomavirus BKV and JCV Epidemiology/Pathology
JC/BK virus–> oral or respiratory infection –> replicaion in oral, GI or upper respiratory tract - PRIMARY VIREMIA
multiplcation in kidneys
TRANSIENT SECONDARY VIREMIA
Immunocompetent–> latent indefinitely in kidneys
Immunosuppression–> reactivation
BK multiplies in urinary tract –> viruria and possible hemorrhagic cystitis
JCV virus viremia–>CNA–> possible progressive multifocal leukoencephalophathy (PML)
How are BKV adn JCV diagnosed?
- PML diagnosed by PCR of CSF or by imaging of brain
- Swollen oligodendrocytes with nuclear inclusions
- DNA analysis of urine, CSF or biopsied tissue for BKV & JCV
- naked DNA
- capsid has fibers (viral attachment ) at vertics
- lytic, persistent and latent infections
- spread in aerosols, fecal matter, close contact, fingers to eyes, inadequately chlorinated swimming pools/ponds
- infect mucoepithelial cells in RT, GIT, conjunctiva/cornea
- may persist in lymphoid tissue (tonsils, adenoids, PP)
- most prevalent <14 yrs and crowded living
- no seasonal prevalence
Adenovirus
How many adenvirus serotypes are know? Which serotypes are militalry personell given a vaccine for?
over 57 serotypes
serotypes 4 and 7 have a vaccine
Name the virus responsible for this combined presentation in young children. What is the name of this presentation?
Adenovirus
- pharyngitis alone in children less than 3 (mimics strep throat)
- pharyngoconjunctival fever in outbreaks – involves older children
- pharyngitis that is often accompanied by conjunctivitis
Name the virus responsible for this symptom. What is the name of this clinical presentation?
Adenovirus
follicular conjunctivitis
Keratoconjunctivitis (among industrial workers)
How is adenovirus diagnosed?
- Virus in throat of patient with pharyngitis (naked with spikes)
- should eliminate streptococcus pyogenes
- infection produces nuclear inclusion bodies
- DNA analysis and immunlolgical probes
- enveloped DNA virus
- use viral DNA polymerase
- cell-to-cell spread and syncytia
- transmitted in saliva, vaginal secretions, or lesion fluid
- no seasonal incidence
- infect/replicate in mucoepithelial cells
- vesicle on erythematous base “dewdrop on a rose petal”
- progression to pustules, ulcers, & crusted lesions
- initially disease at site of infection, then latency
HSV-1 & 2
What are the major differencew between HSV1 & 2? How can they be distinguished?
HSV1 usually transmitted orally whereas, latent in trigeminal ganglia
HSV2 is usually transmitted sexually, latent in sacral ganglia
HTey are distinguishable by molecular and serological tests
> 90% latently infected worldwide but lot few recurrences
they show cross immunity– HSV-1 preinfected show mild HSV-2 disease
What is the name of this presentation and which virus causes it? Why is it particularly concerning?
- herpetic keratitis
- HSV1
- mostly limited to one eye- may lead to recurrent disease
- may lead to permanent scarring, corneal damage, blindless
- HSV-1/-2 infections of eyes/brains has significant morbitity/mortality
Name the virus responsible for this presentation. What is the common name for these lesions? Describe their progression.
- herpes labialis or gingivostomatitis
- Caused mostly boy HSV-1 (HSV-2 ususally causes genital lesions)
- begin as clear vesicles that rapidly ulcerate
- lesions around or throughout mouth, buccal mucose, tongue
- due to febrile illness, lesions called cold sores/fever blisters
HSV-1/HSV-2 Pathogenisis and Reactivation
- initially disease at the site of infection adn then latency
- vesicle on erythematous base
- vesicles then progress to pustules, ulcers & crusten lesions
- eventually latency in the innervating neuron
Reactivaton
- Tirgeminal ganglia for HSV-1, sacral ganglia for HSV-2
- Stress, trauma, fever, UV can reactivate latent virus
- Viruses travel back down the nerve adn caue lesions
- Lesion at same dermatome and location each time
- Generally, vesicular lesions (contain infectious virions)
What is the name for HSV infection of the finger? of the body?
Herpatic whitlow: infectin of fingers (in nurses/physicians ) HSV-1 or HSV-2
Herpes gladiatorum: infection of body (rugby player, wrestlers) HSV-1
A patient presents with seizures, focal neurologic abnormalities and RBC in thier CSF. What is the probably diagnosis?
Herpes encephalitis, usuall caused by HSV-1
Lesions limited to one of the temporal loves
Infection causes destruction of the temporal lobe, which results in RBC in teh CFS
Why is HSV infection of neonates of particular concern? How is it most often acquired?
- no CMI- dissemination to liver, lung and the CNS
- Reesults in death or neurologic dasability, even with treatment
- Acquired in utero or during passage of birth canal (usually HSV-2)
HSV-1 & HSV-2 Diagnosis
- Confirmation by serology (primary infection) or by PCR
- Recurrent infections do not show increase in titers
- Encephalitis: Normal glucose, mildly increase protein, RBC in CFS
- Inclusion bodies (Cowdry type A nuclear inclusions)
- Positive Tzanck Test (syncytia)
What are the important clinical findings shown in the images, and what virus infection do they confirm?
(left) Positive Tzanck Test (syncytia)
(right) Cowdry type A nuclear inclusions
Confirm HSV-1 & HSV-2
- DNA enveloped virus
- acquired from resp droplets or skin
- Infects epithelium in RT, then viremic dissemination
- vesicopustular rash with crop of lesions- on scalp
- Pneumonia in adults/IC patients
- latency in trigeminal ganclia
- Reactivation shows dermatomal pattern
Varacilla Zoster –> herpesvirus
What are the 5 childhood exanthem diseases?
- chickenpox
- Rubella
- Roseola
- 5ths disease
- measels
Chickenpox Epidemiology/Pathology
Fever and maculopapular lesions (rash) after 14 days
within hours lesions form thin-walled vesicles
vesicles on erythematous base (dewdrop on rose petal)
Within 12 hrs vesicles are pustular and begin to crust
Rash spreads to entire body (prevalent on trunk and head)
Lesions last 3-5 days
Name the virus responsible for the shown symptom. Is this disease more sever in adults or children?
- Varacilla Zoster (chickenpox)- Herpesvirus
- primary infection more sever in adults than children
- interstitial pheumonia in 20%-30% or patients– may be fatal
Varacilla Zoster Virus – Herpesvirus Diagnosis
typical rash
serology and genome detection
positive tzank and cowdry type A intranuclear inclusions
- enveloped DNA virus
- spread via close oral or personal contact
- Limited tissue tropism, receptor CR2 or CD21 on B cells
- B-lymphocyte parasite
- positive heterophile antibody test
Eptsin-Barr Virus (EBV, HHV4)
What are the 3 possible outcomesof an Epstein Barr Virus infection? (HHV4)
- Replication in B cells or permissive epithelial cells
- Latent infection of memory B cells in the presence fo CMI
- Can stiumulate adn immortalize B cells
- EBV Pathogenesis
- Classic lympohocytosis increase mononucleara cells)
- Swelling lympoid organs (lymph nodes, spleen, liver)
- Malaise/fatigue – too much energy needed to power T cell resonse
- Sore throat due to EBV in pharyngeal epithelium, tonsils
- Children, less active CMI, thus mild disease
What are the classic triad of symptoms for heterophile antibody-positive ifectious mononucleosis?
What is the viral cause? What are possible complicatiosn of this disease?
Triad:
- lymphadenopathy
- sphenomegaly
- exudative pharyngitis
Extreme fatigue
Caused by EBV (HHV4)
Complications: meningoencephalitis & Gullain-Barre syndrome
What is an additional concern for T-cell deficient patients when they contract EBV (HHV4)?
Significant proliferation of lymphocutes
- polyclonal leukemia (like b-cell proliferative disease & lymphoma)
- associated with African Burkitt lymphoma (endemic lymphoma)
- burkitt’s lymphoma (elsewhere in the world)
- Also associated with Hodgkin lymphoma and nasopharyngeal carcinoma
What virus causes this unusual manifestation? What populaiton would you expect to see this symptom?
EBV (HHV4)
Hairy oral leukoplakia
AIDS patients
EBV Diagnosis
- Clinical picture
- Lymphocytosis (~70%) mnoncytes & atypical lymphocytes (Downey cells)
- Serology to viral antigens and Heterophile antibody test
- DNA enveloped virus
- found worldwide, no seasonal incidence
- spreads cell-to-cell
- spread via blood, organ transplant, saliva, and breast milk
- 90-100% positive at STDY clinics
- promotes T-cell outgroth
- 70-80% positive serotype by 40 yrs
mild pharyngitis adn lymphadenopathy
Cytomegalowvirus (CMV HHV5)
A child is born with small size, thrmobocytopenia, jaundice, microcephaly, intracerebral calcification, hepatosplenomegaly, and rash. The mother was infected by a enveloped DNA virus.
What virus is reponsible for the infant’s symptoms?
CMV (HHV5)
~15% stillborn babies are infected with CMV
~1% all newbornds in US are infected before birth, majority of infections are asymptomatic
CMV and EBV have similar presentations. What are the major differences betweent these two infections?
CMV does not infect B cells and is negative to the heterophile antibody test
Suspect CMV in hterophile (-)ve IM & in hepatitis but not Hep A/B/C
CMV Diagnosis
- IM, negative hetophile antibody test
- Presence owl’s-eye cells (large, intra-nuclear inclusion body surrounded by a halo), serology adn DNA-based methods
- Isolation virus from infant uring durign 1st week postpartum
What do we see a reactivation of CMV in transplant patients? Which transplant is particulary susceptible to failure in patients with a reactivation of CMV? What other symptoms do we see in these patients?
Transplant patients are immunosupressed–> reactivation
CMV can cause kidney transplant failure
Disease in I/C host: pneumonia and pneumonitis
- 1/5 childhood exanthems
- rapid onset of fever of few days followed by rash
- seen on trunk & face, spread and lasts only 24-48 hrs
- transmitted vial saliva
- infects lymphocytes (CD4 T cells)
HHV-6 (6A & 6B) and HHV-7 (roseola)
HHV-6 replicates in salivary glands
An AIDS patient presents with the shown skin lesions. What is the name for these lesions, and what is a probable viral cause? Which cells does this virus infect? How is this virus transmitted?
HHV-8 (Kaposi Sarcoma associated virus)
Polyclonal dark lesions (Kaposi sarcoma)
Infects B cells adn some endothelial cells
Tansmitted sexually, via semen
Diagnosis: clinical picture adn viral DNA in peripheral lymphocytes
- large, complex virus– brick shaped with 2 membranes
- DNA virus, replicates in the cytoplasm
- Carries proteins form genome replication
- contagious human-human droplets or skin contact
- replicates in URT, spread via lymphatic & viremia
- Infects internal and demal tissues after 2nd, more intense viemia
- simultaneous eruption of hemorrhagic, crater form lesions (first in mouth, then on body)
- 5-17 day incubatin period
- high fever, fatigue, severe headache, bachache, malaise
Variola (smallpox)
- large, complex virus– brick shaped with 2 membranes
- DNA virus, replicates in the cytoplasm
- Carries proteins for genome replication
- slow, developing infection – lesins with small dimple in center (not itchy or painful)
- spreads via direct contact or fomites
- genital lesions spread during sexual contact
- replicates in URT, spread via lymphatic & viremia
- mostly AIDS associated
Moluscum Contagiosum Virus (Poxvirus)
Variola (Smallpox) Diagnosis
- clinical picutre, but can be confirmed by culture
- infected cells contain a cytoplasmic Guarnieri inclusion body
What is the viral cause for this clinical presentation? What strain of this virus was used for vaccine production?
Variola (Smallpox)
Vaccinia (strain cowpox) used for vaccination
Immunocompromised patient presents with shown skin lesions. Lesions are not itchy nor painful. What is the most probable viral cause for the indicated symptom?
What is another diagnositic criteria for this disease?
Molluscum Contagiosum Virus (Poxvirus)
Diagnosis: Large, eosinophilic inclusions in epithelial cells
- enveloped DNA virus
- transmitted via blood, needlesm sexually or perinatally
- viral genome frequently in hepatocarcinoa cells
- Rash and arthritis
- anorexia, nausea, vomitig, pain in URQ & abdomen
- among smokers, distaste for ciagrettes
- dark urine and jaundice
- acure or chronic infection
Hepatitis B virus
Hep B pathology
- virus infects hepatocytes
- CD8 T cells lyse HbsAg expression hepatocye
- immune complexes can cause a rash and arthritis
- after a few days, dark urine and jaundice (yellow skin & eyes)
- chronic hep b infection may lead to cirrhosis & risk for carcinoma
- co-infection with HepD promotes fulminant hepatitis
Patient presents with illulstrated symptoms. Viral cuase is an enveloped DNA virus. What is the viral cause? What are other diagnositc criteria for this virus?
Hep B
Diagnosis: clinical pictue (jaundice ) & elevated ALT/AST/AP/bilirubin
Confirms icterus not etiology – serology is very useful
