Prions and DNA Viruses II Flashcards
what are the charateristrics of Varicella Zoster Virus (HHV3)?
- enveloped
- lifelong infection (shingles/chickenpox)
- very widespread before vaccine era
- inhalation of aerosols of skin lesions
- infects RT, then disseminated via T Cells??
- produces a vesiculopustular rash with crops of lesions
when is HHV-3 contagious?
From the first day of symptoms until last blister is crushed
recall last it spreads via aerosols on the skin lesions
Where is the latency location of HHV-3?
Trigeminal Ganglia
THese are sensory neurons. Reactivation with shingles shows dermatomal patter (think of shingles).
Chicken Pox: Symoptoms and Characteristics
- VZV
- childhood exanthems (1/5)
- Fever and a maculopapular lesions (rash) after ~14 days
- Vesicles on an erythematous base
- vesicles turn pustular and start to crush (within 12h)
- itchy
exanthem=childhood rash
The other four are rubella, roseola, 5th disease, measles.
Pattern of Chickenpox Spread
Back of head and ears then spreads centrifugally
Key point: Chickenpox is also on the scalp, which is absent in many other diseases.
centrifugal spread: spreading down the neck to the upper extremities, trunk, and finally the lower extremities,
Scratching and Chickenpox may cause?
bacterial superinfection
VZV and immunocompromised individuals
- more severe illness (Progressive, prolonged, high mortality)
- Visceral Involvement: encaphalitis, nephritis, pneumonia, hepatits
ENPP for VZV in Immunosuppressed
Herpes Zoster
- painful lesions (not itchy) from reactivation of virus from sensory neurons
- reactivation mostly in elderly
- Post-herpetic neuralgia – pain months to years after zoster.
The pathogens may switch between the latent and lytic cycles, and a process in which a latent virus enters the lytic stage is known as reactivation
Postherpetic neuralgia (post-hur-PET-ik noo-RAL-juh) is the most common complication of shingles. It causes a burning pain in nerves and skin. The pain lasts long after the rash and blisters of shingles go away. The risk of postherpetic neuralgia rises with age.
Post-herpetic neuralgia
pain months to years after zoster
Postherpetic neuralgia (post-hur-PET-ik noo-RAL-juh) is the most common complication of shingles. It causes a burning pain in nerves and skin. The pain lasts long after the rash and blisters of shingles go away. The risk of postherpetic neuralgia rises with age.
VZV Prevention Measures
- **isolate until last blister crushed **
- clean skin
- immunization: chickenpox (children) / zoster (adults)
Diagnosing VZV
- Positive Tzanck Test
- Cowdry Type A intra-nuclear inclusions
- rash
- serology and genome detection (systemic and neuronal)
In dermatopathology, the Tzanck test, also Tzanck smear, is scraping of an ulcer base to look for Tzanck cells. It is sometimes also called the chickenpox skin test and the herpes skin test. It is a simple, low-cost, and rapid office based test.[1]
Tzanck cells (acantholytic cells) are found in:
Herpes simplex[2]
Varicella and herpes zoster
Pemphigus vulgaris
Cytomegalovirus
Cowdry Test
Cowdry bodies are eosinophilic or basophilic[1] nuclear inclusions composed of nucleic acid and protein seen in cells infected with Herpes simplex virus, Varicella-zoster virus, and Cytomegalovirus.
There are two types of intranuclear Cowdry bodies:
Type A: herpes simplex, VZV, and measles
Type B: poliovirus, CMV and adenovirus
Epstein Barr Virus (EBV, HHV4)
- Enveloped
- DNA
3.infections worldwide (mostly asymptomatic) - oropharyngeal secretions (kissing or personal contact)
- *Limited tissue tropism, VAPs help bind B cells & tonsil epithelium
- primary infection- tonsil epithelium and** B Cells**
VAP- vascular adhesion protein
Human Herpes Virus 4 (HHV4)
Epstein-Barr worldwide prevalence
- more than **90% seropositive **
- most by age 2 in developing countries
- vs. late childhood/adolescence in developed countries
infection is delayed by 2nd decade of life, results in Infectious Mononucleosus in 50%
Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis, but other viruses can also cause this disease. It is common among teenagers and young adults, especially college students. At least one out of four teenagers and young adults who get infected with EBV will develop infectious mononucleosis.
What are the three potential outcomes of Epstein Barr (EBV, HHV4)?
- replication in epitehlial cells (tonsils and B Cells- site of primary infection)
- latent infection of memory B Cells
- stimulate and immortalize B Cells (various lymphomas)
- To summarize current understanding of that interaction, primary infection occurs by the oral route and leads (i) to local virus replication in the oropharynx, involving lytic infection of mucosal epithelium and possibly also local B cells, and (ii) to a virus-driven growth transformation of B cells in pharyngeal lymphoid tissues, followed by a switch to a truly latent (antigen-negative) infection of the generalized memory B cell pool [2]. While these events are most clearly seen during primary infection, they are also on-going during the subsequent carrier state; thus, virus reactivating from the B cell reservoir is thought to seed both new foci of replication in the oropharynx, leading to recurrent low level shedding of infectious virus, and new growth-transforming B cell infections. A large body of evidence suggests that these lytic and growth-transforming latent infections are subject to T cell-mediated immune control both during primary infection and throughout life [3]. Thus, some primary EBV infections are clinically manifest as infectious mononucleosis (IM), a febrile illness characterized by hyper-expansion of both lytic and latent antigen-specific T cell responses, while lower levels of these same responses persist as memory T cells in the blood of all virus carriers and indeed are enriched as tissue-resident populations in oropharyngeal lymphoid tissues where EBV reactivations are thought to initiate [4,5].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597738/
EBV Pathogenesis- see slides 60-61
https://www.ncbi.nlm.nih.gov/books/NBK470387/#:~:text=After%20exposure%2C%20the%20EBV%20infects,lymphadenopathy%2C%20tonsillitis%2C%20and%20hepatosplenomegaly.
Classic Lymophocytosis
- swelling in lymohoid glands
- malaise/fatigue (too much energy needed to power the T-Cell Response)
- sore throat- pharyngitis/tonsilitis
EBV
Why do children have milder disease?
less active CMI
Heterophile Antibody-Positive Mononucleosis
- EBV
- large increase in monocytes (hence mononucleosis)
- High fever (febrile) and Malaise/Fatigue
- complications include: meningoencephalitis & Guillain-Barré syndrome.
- Triad of symptoms: lymphadenopathy, splenomegaly, pharyngitis.
The infection of the B-lymphocytes results in the production of immunoglobulins (heterophile antibodies).
After exposure, the EBV infects the epithelial cells of the salivary glands and the oropharynx. Lymphocytes residing in the tonsils get exposed to the virus and then enter the bloodstream. Lymphoid hyperplasia is common and may be seen as generalized lymphadenopathy, tonsillitis, and hepatosplenomegaly.
https://www.mayoclinic.org/diseases-conditions/guillain-barre-syndrome/symptoms-causes/syc-20362793
Lymphoproliferative Disease
- EBV
- may be fatal in T-Cell Deficient inds. ??
- polyclonal leukemia
- assoc. with African Burkitt Lymphoma (malaria is a co-inducer)
- Hodgkin lymphoma, Burkit lymphoma, nasopharyngeal carcinoma.
Hairy Oral Leukoplakia
- EBV
- hairy looking white patches.
- Mostly on the tongue and in the mouth of AIDS patients.
an interesting side note: this can cause death in 24-52 months. Very serious.
EBV: Diagnosis
- Lymphocytosis (70% Monocytes) and atypical lymophocytes
- serology test for viral antigens
- (+)vs Heterophile antibody test
note the presence of Downey Cells (activated T cells)
Cytomegalovirus (CMV, HHV5)
- DNA
- enveloped
- ~1% newborns & 70-85% adults infected by age 40.
- Spread via close personal contact including sexual contact.
- ↑ in saliva, cervical secretions, semen, urine, blood, breast milk.
- likely a majot STI
**commonly associated with salivary glands
human herpes virus 5
https://www.ncbi.nlm.nih.gov/books/NBK459185/
Cytomegalovirus - Mode of transmission
CMV Diagnosis
- Infects/Activates T Cells (NOT B Cells), therefore heterophile antibody test will be negative
- Presence of owl’s-eye cells
- serology and DNA-based methods.
- Isolation of virus from infant urine during 1st week postpartum.
Owl’s eye cells: Large intra-nuclear inclusion body surrounded by a halo.
HSV-6 (6A and 6B) and HSV-7
- ubiquitous
- Mostly HHV-6B & occasionally HHV-7 cause exanthem subitem.
exanthem subitem: It’s also known as sixth disease, exanthem subitum, and roseola infantum. It is usually marked by several days of high fever, followed by a distinctive rash just as the fever breaks.
Variola (smallpox)- disease progression
Variola Diagnosis
- diagnose with clinical picture
- confirm with culture
**Infected Cells- cytoplasmic Guarnieri inclusion body
smallpox vs chicken pox
Monkeypox Virus
- acquired from respiratory secretions & infected skin lesions
- passed via sex but not STI
- smallpox vaccine confers protection (why?)
- less severe than contagious that smallpox
How does Molluscum Contagiosum Spread?
- direct contact or fomites, more often in children
- genital lesions transmitted sexually in adults
Can infect any part of skin – may be AIDS-associated
Molluscum Contagiosum Virus: Lesion Characteristics
- self-limiting infection of epithelial cells
- Nodular elevated lesions with a tiny dimple in the center
- not itchy or painful
self-limiting- can be treated at home
HBV Replication
