Viral Exanthemas + HSV1/2 + VZV Flashcards

1
Q

Compare the structure of the Parovirus B19 and HHV6 and 7.
• what are do they have in commmon?

A

Parvovirus B19 (“Fifth Disease”)

Structure
Non-enveloped, ssDNA virus (simplest DNA virus)

Human Herpesvirus 6 and 7 (Roseola)

Structure
Enveloped large dsDNA virus

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2
Q

Compare and contrast the following Viruses with Respect to their structure.

A
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3
Q

What is the pathogenic mechanism of Parvo B19?
• what is the timing in the process?
• How does the mechanism correspond to symptoms?

A

Pathogenic Mechanism
Infection of RBC precursors and replication in these cells leads to progressive anemia throughout this disease. Infections of these cells is Bi-phasic:

1. Lytic Phase/Infectious phase – causes cytokine release and prodromal symptoms starting ~7days post-exposure

2. Non-infectious Immunologic phase – in this phase the immune response results in IgG production to neutralize the virus. It is in this phase that RASH and ARTHRALGIA presents from CELL-MEDIATED responses.

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4
Q

Who is at the highest risk of dying from Parvo B19?
• what symptoms present in these people?

A

Mortality
• This disease can have a profound impact on people with Heriditary Spherocytosis and Sickle Cell anemia leading to APLASTIC anemia in these people.

• Immunocompromised people may have persistent infection that leads to **Chronic Anemia

• Trasplacental Transmission**
is also risky with 5% of cases resulting in miscarriage/HYDROPS FETALIS.

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5
Q

How common is Parvo B19?

A

50% of adults are seropositive

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6
Q

How is Parvo B19 transmitted? Disease Caused?
• When does it replicate?
• What is the structure of Parvo B19?

A

Erythema Inectiosum - Parvovirus B19 (“Fifth Disease”)

Structure
Non-enveloped, ssDNA virus (simplest DNA virus)

Transmission
Respiratory Tract Secretions, Exposure to Blood products, Mother to Fetus

Replication Cycle
Depends on S-phase in RBC precursors (NOT mature RBCs) of host to replicate

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7
Q

What are the Key findings in Parvo B19 infections?

A

Key findings/Diagnosis
Slapped Face Rash on the cheeks and reticular body rash on children 1-2 wks after exposure. Arthralgias in adults.

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8
Q

Paramyxoviruses – Measles (Morbilivirus)
Structure?
How is it spread?
How contagious is it?

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Transmission
EXTREMELY CONTAGIOUS spread via respiratory route
Requires a population size of more than 100,000 ppl. That is provided by undervaccination

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9
Q

Measles
• Structure
• Family
• What two factors make it different than other viruses in the family?

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Replication Cycle
2 factors separate measles from the rest of the Paramyoviruses:
1. Receptor usage - MV receptors are CD46, SLAM and nectin-4 and separate H (hemagglutinin) and F (fusion) proteins. (H and F are important to establishing persistent infection in the CNS)

  1. Formation of intracellular inclusion bodies
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10
Q

How does measels present?
• Pathognomoic lesion?
• Structure?

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Disease Presentation
Morbilivirus typically sits latent for 10-14 days after exposure then the patient get the 3C’s cough, coryza, and conjunctivitis along with high fever (101-105). Photophobia may result in this time due to conjunctivitis. Pathonognomic for measles are KOPLIK SPOTS (white spots on the inner cheek that occur before rash). About 2-3 days after symptoms onset a rash appears in accordance with the peak CD8+ T-cell proliferation (cell mediated response). So rash indicates that the virus is clearing.

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11
Q

Measles
• affect on immune function?
• Structure?

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Pathogenic Mechanism
1. This virus has the ability to SUPPRESS immune function probably by infecting MONOCYTES specifically delayed-type hypersensitivity responses (false negative TB skin test). Suppression of immune function occurs just before the rash starts and persist for ~1 mo.

  1. Also antibody production and cellular immune responses to new antigens are also impaired
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12
Q

Measles
• Who gets them?

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Epidemiology
Typically an infection of Children (kills 150K per year)

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13
Q

Measles
• Prophylaxis
• Structure

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Treatment
If MMR vaccine is given within 6 days of exposure course of the disease may be improved

Vaccine is live attenuated and gives life-long immunity. Administration occurs 12-15 mo. (must be > 6 mo to avoid maternal ab interference) and at 4-6 year old. (note: kids would therefore be most susceptible btwn 6-12 mo w/o maternal abs or their own)

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14
Q

Measels
• why is the vaccine so effective?
• Structure?

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Vaccine efficacy is related to viruses being ANTIGENICALLY STABLE and MONOTYPIC (aka abs produced against 1 virus are protective against all)

Disease could be eradicated because: only 1 serotype, clinically identifiable, no animal reservoirs.

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15
Q

Measels
• What typically kills people?
• What other complications could occur?
• When do they occur?

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Mortality
Death by this virus is typically due to superimposed Bacterial Pneumonia

Autoimmune demyelination is not uncommon (1/1000) may also occur Acute disseminated encephalomyelitis (ADEM) or postinfectious encelphalomyelitis (PIE) may also occur in 3 wks following infection leading to CONVULSIONS, DEAFNESS, and RETARDATION

Persistent infection in the brain (from H and F mutations) may lead to:
Encephalitis (inclusion body (5 mo later) and subacute sclerosing (7 years later)) may also occur.

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16
Q

Measels
• What are some key things you’re looking for?
• Structure?

A

Paramyxoviruses – Measles (Morbilivirus)

Structure
Enveloped, Negative-sense, ssRNA

Key findings/Diagnosis
Defined Clinically as a generalized rash lasting more than 3 days, with a temperature above 101 F and the 3 C’s cough, coryza, and conjunctivitis + KOPLIK’s SPOTS on bucal mucosa

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17
Q

Rubella
• Transmission: how and when can it occur?
• Structure

A

Rubella - Togavirus

Structure
Enveloped positive-sense ssRNA

Transmission
Primarily Aerosols
Viral Shedding of particles lasts for 1 month after initial exposure (~week after the rash is gone)

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18
Q

Rubella (Togavirus)
• How does it present?
• Structure?

A

Rubella - Togavirus

Structure
Enveloped positive-sense ssRNA

Disease Presentation
Rubella (togavirus) typically incubates for ~1 week. Mild disease characterized by low-grade fever, occasional conjunctivitis, LAD. A little over 2 weeks later (16-21 days) a Morbilliform Rash that starts on the face and spreads.

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19
Q

Rubella (Togavirus)
• Who suffers the most severe consequences of this infection?
• Structure?

A

Rubella - Togavirus

Structure
Enveloped positive-sense ssRNA

Mortality
THE MOST SERIOUS CONSEQUENCE OF RUBELLA IS FOR THE FETUS IN 1st and 2nd Trimesters of Pregnancy. Virus crosses the placenta and replicates in all tissues and organs. Result is severe neurological deficits and cataracts.

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20
Q

Rubella
• Where can you isolate virus from?
• Structure?

A

Rubella - Togavirus

Structure
Enveloped positive-sense ssRNA

Key findings/Diagnosis

Virus can be isolate from Stool (make sense b/c its enveloped) and nasopharynx

21
Q

Picornavirus (family)
• what groups are in this family?
• what makes them distinct from rhinovirus?

A
  • *Picornavirus**
  • *General: 4 groups Poliovirus, Coxsackievirus, Echovirus, Enterovirus.** These are differentiated from rhinovirus by 2 main factors: Acid Stability and Less Stringent Growth Requirement (both human and primate at 37 C).
22
Q

Picronavirus
• what makes enterovirus different from the others in this family?

A

Enterovirus humans are the ONLY known reservoir.

23
Q

Picornavirus
• Structure?
• Transmission?

A

Picornavirus

Structure
Non-enveloped positive sense ssRNA

Transmission

  • *Oral-Fecal** route (enterovirus and Coxsackie)
  • *Aerosol** contamination of Fomites (Coxsackie)
24
Q

Picornavirus
• In what two ways can it present?
• How does presentation depend on serotype?

A
  • *Picornavirus**
  • *General: 4 groups Poliovirus, Coxsackievirus, Echovirus, Enterovirus**

Disease Presentation

***DISEASE OCCURS PRIMARILY IN THE SUMMER AND FALL (MAY-NOV)**
Incubation typically occurs for 2-10 days followed by a somewhat bisphasic illness that consists first of flu-like symptoms then stiff neck and headache about 1 week later (~18 days post infection).

Hand, Foot, and Mouth Disease:
• Caused by Coxsackievirus A16, A6 and enterovirus 71; presents as ulceration of tonsils and uvula (herpangia) along with abdominal pain and flu-like symptoms. Disease gets its name from vesicular lesions on the hands and feet.

25
Picornavirus • what tissues does it invade? • How long does transmission remain and issue? • Structure?
* *_Picornavirus_** * *General: 4 groups Poliovirus, Coxsackievirus, Echovirus, Enterovirus** _Structure_ **Non-enveloped positive sense ssRNA** _Pathogenic Mechanism_ Initially enteroviruses replicate in **lymph of URT** (tonsils, lymph nodes) and gut (**Peyer’s patches**). Eventually its spreads to **blood (viremia) and infection of spinal cord, brain, meninges, myocardium**, and skin. *Persistence of this infection may be related to its ability to cause asymptomatic infection and its persistence in the stool for several weeks after infection resolves*.
26
Hand Foot Mouth syndrome • Mortality? • Virus Structure?
* *_Picornavirus_** * *General: 4 groups Poliovirus, Coxsackievirus, Echovirus, Enterovirus** _Structure_ **Non-enveloped positive sense ssRNA** _Mortality_ Hand, Foot, and Mouth: **Self-limiting disease** that requires only symptomatic management (highly contagious)
27
Picornavirus • How long will cultures stay positive after infection with something like Hand, Foot, and mouth?
* *_Picornavirus_** * *General: 4 groups Poliovirus, Coxsackievirus, Echovirus, Enterovirus** _Structure_ **Non-enveloped positive sense ssRNA** _Mortality_ Hand, Foot, and Mouth: **Self-limiting disease** that requires only symptomatic management (highly contagious)
28
Does Mumps cause a rash?
NOOOO
29
Mumps • Structure • Transmission
**_MUMPS (Paramyxovirus)_** _Structure_ Helical, negative sense ssRNA, nonsegmented _Transmission_ Less infectious than measles (aerosol) Virus shed in saliva ~6 days *before onset of clinical disease* (key to it spreading)
30
Mumps • Presentation • Structure
**_MUMPS (Paramyxovirus)_** _Structure_ Helical, negative sense ssRNA, nonsegmented _Disease Presentation_ Incubation typically is **18 days** before you start to see the **first clinical sign of swelling in the parotid** (chipmunk). **Aseptic meningitis** may result in the 50% of pts that have viral replication in CNS. This may result in **deafness.** **Gonadal involvement** may occur in post-pubertal men.
31
Mumps • Morbidity • Structure
**_MUMPS (Paramyxovirus)_** _Structure_ Helical, negative sense ssRNA, nonsegmented _Mortality_ Deafness is an important morbidity, as is Testicular enlargement (3-4x normal size)
32
HSV-1 and HSV-2 • Structure
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus
33
VZV • Structure
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus
34
HSV-1/2 and VZV • In what places do that establish infection? • Where does latency occur for each type?
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Replication Cycle_ Like all herpes viruses can replicate in 1epithelial cells then 2lymph node then in they can move into 3neurons and establish latency. Neurotropism for **HSV-1 = Trigeminal** N; **HSV-2 = Sacral and Lumbar**; **VZV = dorsal root**
35
Describe the HSV1/2 and VZV Lytic Cycle. • Structure
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus **LYTIC CYCLE** 1Herpes virus *electrostatically* binds **heparin sulfate** (on host cell surface proteoglycans). *2Lock and key* interactions between the HV and host cell surface proteins leads to fusion of the envelope and host membranes. **3Nucleocapsid is then transported to the nucleus**. 4HV uses **Immediate Early transcription factors** to *redirect host RNA polymerase* read the viral DNA and **transcribe RNA for the early proteins** (**DNA polymerase, and Thymidine kinase** etc.). 5Early protein RNA is made by ribosomes and imported BACK INTO the host nucleus. The **HERPES DNA pols and thymidine kinase are then used to make more copies of the HV.** 6At this point the RNA for **late proteins** starts getting synthesized and **LATE PROTEINS (structural proteins) are produced** and *imported back into the host nucleus*. 8**Assembly** of virions can now occur and **exocytosis** happens the usual way (ER à Golgi à Membrane fusion). 9As virions fuse with the membrane they **leave behind HV membrane proteins** that are on their outer envelope. **10Giant cells can now be created by one endothelial cell grabbing onto the next with herpes proteins.**
36
Where does the Herpes Virus Carry out its life cycle? • Structure.
the entire herpes life cycle occurs in the **nucleus** and the only thing that occurs outside is protein synthesis b/c no ribosomes in nuc.
37
How does the Herpes Virus move through your nerves?
We assume the same happens in Neuronal virus transmission but in this case the **PROGENY ARE TRANS SYNPATICALLY TRASPORTED IN A RETROGRADE FASHION TOWARD CNS** (but don’t actually get there)
38
Herpes • What is required for latentcy? • How do HSV-1/2 and VZV maintain latency?
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus **LATENT CYCLE** This occurs soon after the initial infection. The latent cycle consists of 3 phases: *Establishment, Maintenance, and Reactivation.* To maintain latency the virus must: prevent lytic phase, prevent neuronal apoptosis, and evade immune surveillance. HSV does all of this by the **LAT protein** that has **NO PROTEIN PRODUCT,** but **makes micro-RNA** that: 1**represses viral gene expression, 2prevents apoptosis, 3impairs CD8+ function.** NOTE: VZV does NOT encode LAT protein (we don’t know how it lays latent)
39
HSV-1 and HSV-2 • Transmission • Structure
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Transmission_ Saliva and Genital Secretions
40
HSV-1 and HSV-2 • Clinical presentation of both primary and secondary infection • Structure?
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Disease Presentation_ *Primary infections are often not observed*, but when they are they are *more severe* than subsequent secondary infections. Recurrent infections often occur *5-8 times per year* and produce blisters on an erythematous background. For HSV-1 these may be located on **skin**, **eyes**, or **cause encephalitis (via opthic n. involvement)**. For HSV-2 urogenital and meningitis involvement is most common. Stress and Sunburn are often causes of relapse due to **reductions in cell mediated immune surveillance. When these do recur they stay local due to high levels of HV ANTIBODIES.**
41
HSV-1 and HSV-2 • How does the epidemiology differ?
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Epidemiology_ 55% of adults have HSV-1 20% of females have HSV-2; 10% of males have HSV-2
42
HSV-1 and HSV-1 • Who dies from it? • Structure?
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Mortality_ **Neonates and Immunocompromised** patients are at greatest risk of getting **CNS involvement** that can be **fatal.**
43
HSV-1 and HSV-2 • How do you diagnose someone with it?
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Key findings/Diagnosis_ Dx: Clinical; serology is ONLY USEFUL for Primary Infections; **CONTRETE DX** is need in suspected HV **meningitis** à Use **PCR** (culture rare); **Tzank Smear** à taken from vesicle shows multinucleated giant cells
44
Varicella Zoster (VZV) • transmission • Structure
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus **_Varicella-Zoster Virus_** _Transmission_ AEROSOL
45
Varicella Zoster • Presentation: Primary and Secondary
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Disease Presentation_ * *Primary infection** usually occurs in the Late winter/Early Spring and sits latent for about 14 days before you see Chickenpox presentation (Fever + Itchy rash on scalp and trunk). Adult primary infections are more severe and may result in pneumonia. * *Reactivated infections** cause shingles that results in pain and rash (different from primary rash – not the case in HSV) along a thoracic dermatome or forehead (dangerous). 2 to 4 weeks later rash resolves but pain often persists à Postherpetic neuralgia.
46
``` Varicella Zoster (VZV) • Where does infection set in? • How and when does it spread? ```
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Pathogenic Mechanism_ Conjunctiva or URT get infected (day 0) à Viral replication in regional lymph nodes à Primary Viremia (day 4-6)à viral replication in liver and spleen à secondary viremia à Chickenpox (day 14)
47
Varicella Zoster • Who's been exposed? • Structure?
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Epidemiology_ 99% of people have antibodies to it
48
``` Varicella Zoster (VZV) • Diagnosis? ```
**_Herpes Simplex 1 and 2 (HSV 1 & 2) + VZV_** _Structure_ Herpesvirus so…Enveloped large linear dsDNA virus _Key findings/Diagnosis_ Dx: **Clinical**; **Tzanck Smear** can be used