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HD-Virology
Exanthemous Viral Infections
49
Medical
Graduate
12/06/2010

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Term

Variola Virus

Smallpox Clinical Syndromes

Definition

5-17 day incubation period, there is high fever, fatigue, headache, backache, and malaise followed by rash in mouth and then body. Vomiting, diarrhea, and excessive bleeding soon follow. The simultaneous outbreak of the vesicular rash distinguishes it from varicella-zoster which erupts in successive crops. 

Term

What diseases are caused by Variola?

 

Definition
Small pox and Molluscum Contagiousum
Term

Variola Virus


Diseases contracted by farm animal handlers.

Definition

Orf (peudocowpox) - (poxvirus of sheep and goats) resulting from direct contact w/ animal lesions. A single granulomatous lesion forms.

 

Vaccinia (Cowpox) - A single nodule appears at point of contact and is hemorrhagic

 

 Lesions can be mistaken for anthrax and usually regress in 25-35 days. 

Term
What is the structure of Variola virus?
Definition

Largest of the DNA viruses (230nmx300nm). Ovoid or brick shaped with a membrane-enveloped core, lateral bodies and an outer membrane envelope. 

Carry enzymes such as DNA dep RNA pol.

Circular ds DNA Chromosome.

Term
Describe the replication of Variola.
Definition

It is unique to other DNA viruses in that it replicates entirely in the cytoplasm. Replicates in inclusion bodies called "Gaurnieri."

After the virus enters the cell, the packaged-enzyme uncoatase removes the membrane around the core.

Viral core has RNA pol, polyadenylate and capping enzymes, and transcription initiators.

Term
Describe the pathogenesis of Variola
Definition

It is contracted through inhalation-> Replicates in the upper respiratory tract (asymptomatic)-> moves into the lymphatics through infected macrophages-> disseminates to the lymph nodes, spleen, liver, bone marrow and skin through Secondary Viremia-> Causes hemorrhaging of small blood vessels in the dermis giving rash and pox.

This virus also produces proteins which reduce the production of IFN and Ab's, and it will spread from cell to cell to avoid detection by the immune system. 

Term
Describe Molluscum Contagiosum.
Definition

Develops due to direct contact with lesions. A lytic infection develops, and it created small wart-like lesions that do not spread extensively.

These lesions are typically found on the trunk, genitals and extremities.

Incubation time is 8-20 weeks.

Term
What disease does Parvovirus cause?
Definition

"Fifth disease"

erythema infectiosum

Caused by B19.

Term
What is the structure of Parvovirus?
Definition

 

  • Smallest of the DNA viruses (18-23nm).
  • It is nonencapsulated-icosahedron, with a single ssDNA genome. 
  • These genomes can packaged as either + or -sense
  • The genome encodes 3 structural and 2 nonstructural proteins

 

Term
Describe the replication of Parvovirus.
Definition

 

  1. Parvovirus has receptors of the blood group P antigen on erythroid precursors, mediating its entry and uncoating.
  2. The ssDNA is then taken to the nucleus.
  3. The complimentary strand will only be synthesized if the cell is in S phase (some necessary factors are present)
  4. The ssDNA has an IRS sequence (inverted repeat sequence) that will fold over to serve as the primer for DNA pol→dsDNA
  5. The 2 nonstructural and the 3 structural proteins (VP1, VP2 and VP3) are made in the cytoplasm.
  6. Packaging is completed upon cell lysis.

 

Term
Describe the "biphasic" pathogenesis of B19 Parvovirus.
Definition

  • Phase 1: the febrile stage, and the patient is infectious. The viruses replicates in the upper respiratory tract and erythroid cells in the bone marrow. This is the first week of infection, and the production of erythrocytes in halted. After 8 days, a large viremia occurs, releasing virions into the oral and respiratory secretions.
  • Phase 2: this "symptomatic phase" is mediated by antibodies, and B19 is eliminated. The symptoms are rash and arthralgia (painful joints).  

Term
Why does parvovirus infect erythroid precursors rather than RBC's?
Definition
Parvovirus has receptors for the P antigen on erythrocytes. The virus needs host machinery to replicate, and RBC's do not have nuclei!
Term
Describe the epidemiology of Erythema Infectiosum
Definition

  • 65% of the adult population had contracted B19 by age 40.
  • The disease presents as erythema infectiosum in children and as arthralgia and arthritis in adults.
  • Spread by respiratory droplets and oral secretions

 

Term

 

  1. Clinical Syndromes: Erythema infectiosum
  2. In Adults?
  3. Aplastic Crisis. Who should be concerned?
  4. Hydrops fetalis

 

Definition

 

  1. For first 7-10 days, it is prodromal with no symptoms(contagious). Culminates in "slapped appearance" on the cheeks and subsides in 1-2wks.
  2. Polyarthritis (rarely get the rash).
  3. Hemolytic anemia cases, such as Sickle-cell patients, can be at risk of complete decimation of their erythrocytes=reticulocytopenia. This syndrome is caused by a combination of the killed erythroid precursors by B19, and the fact that their cells already have the tendency to hemolyse (anemia)
  4. Is anemia and heart failure of a fetus. This occurs when B19 crosses the placenta of a seronegative mother. No effect on seropositive mothers.

 

Term
How is parvovirus diagnosed/treated?
Definition

Diagnosis is made by clinical presentation.

There is no treatment.

Term
Paramyxoviruses all share the ability to:
Definition
Form syncytia.
Term
What are two paramyxoviridae members?
Definition
Measels virus and Mumps virus
Term
Describe the structure of the measles virus?
Definition

  • There is a (-) sense ssRNA associated with: nucleoprotein (NP), polymerase phosphoprotein (P) and large protein (L).
  • F promotes fusion to membranes, hemolysis and viral entry. Requires proteolytic cleavage for fusion of membranes.
  • Hemagglutinin-neuraminidase (HN), hemagglutinin (H) and G promote viral attachment. 
  • Note: it will always be F with one of the other 3.

Term
Describe the replication of measles virus (we only have to know measles, not mumps).
Definition

  1. HN, H or G will bind to a sialic-acid residue on a glycoprotein= either CD46 (a protein which inhibits complement fixation on self) or CD150 SLAM (signaling lymphocyte activating molecule- which regulate TH1 and TH2 responses). Measles disrupts the function of both.
  2. RNA pol is part of the nucleocapsid, and replication takes place in the cytosol. Copies several mRNA and full-length (+)ssRNA (that serve as templates for the synthesis of (-) ssRNA that is packaged).
  3.  Genomes then associate with L, N, and NP to form nucleocapsids which associate with M (matrix) protein on viral glycoprotein-modified PMs. Mature virions then bud.

Term
Describe the epidemiology of Measles virus.
Definition

In unvaccinated areas, it is a common disease-> can be deadly

Before 1960, 90% of US population got it.

It is passed through respiratory droplets.

Term
Pathogenesis of Measles virus.
Definition
[image]
Term
Outline the basic clinical course of the Measles.
Definition

 

  1. 7-13 day incubation period where the patient has typical CCC and P (cough, coryza, conjunctivitis and photophobia) of a bad cold
  2. 2 days after this, Koplik spots appear on the buccal mucosa (near molars on inside of cheeks). Described as grains of salt surrounded by a red halo. Lesions subside in 1-2 days.
  3. 12-24 hours after Koplik spots, exanthema erupts (Maculopapular rash) beneath ears and will cover the entire body in 1-2 days. Fever is highest now.

 

Term
What are the serious complications that Measles can cause?
Definition

  1. Giant cell pneumonia without a rash in T Cell-deficient children.
  2. Encephalitis - rare (0.5%), but 15% mortality - is caused by: 1.) direct infection of the neurons, 2.) Post-infectious encephalitis= immune-mediated 3.) Subacute Sclerosing Panencephalitis (sspe)= caused by a defective measels virus produced during the acute phase (neurologic problems worsen over the years after the infection).
  3. Atypical measles is caused by prior sensitization with insufficient protection (people who received older inactivated vaccination). This can enhance the immunophathogenic response to wild measles virus. The illness begins abruptly and is more intense. 

Term
How is measles diagnosed,
Definition

Usually done easily upon inspection.

You can also see syncytia with Giemsa staining.

There is also a 4x increase in measles Ab in titer.

Term
What is the treatment for measles?
Definition

Most children are given an attenuated live virus before age 2 along with mumps and rubella (MMR).

Since there is only one serotype for this disease (it only infects humans), it is a good candidate for eradication. 

There are no antiviral treatments.

Term

What disease does Rubella virus cause?

What Class is rubella in?

What is the model virus for this class?

Definition

German Measles

Togavirus

Alphavirus

Term
Outline the Replication Cycle of Togavirus (same for rubella and alpha).
Definition
[image]
Term
What is the structure of Alphavirus?
Definition

+ssRNA within an icosahedral capsid.

Has an envelope that is very tight due to the membrane glycoprotein C terminus interacting with the capsid, taking on the icosahedral shape.

45-75nm

Term
How are most Togaviruses spread (including Alphavirus)?
Definition

They are zoonoses typically spread by arthropods

Live in many animals.

Term
Describe the replication of Alphavirus.
Definition

  1. The virus enters the cell by R' mediated endocytosis.
  2. The viral membrane fuses with the endosomal membrane once the endosome becomes acidic
  3. the (+)ssRNA acts as mRNA and binds to ribosomes
  4. The first 2/3 of the genome (42S early RNA) are synthesized as 4 individual proteins: NSPs 1-4 (nonstructural proteins) Which are components of the RNA pol.
  5. The RNA pol synthesizes the last 1/3 of the genome (26S late RNA) which encodes the E1-E3 membrane glycoproteins, the capsid (C) proteins.
  6. The RNA pol also synthesizes new copies of the (+)ssRNA genome
  7. The C proteins (1st) and E proteins are assembled and glycosylated in the ER. 
  8. The capsid is released from the ER, where the C proteins interact with the ssRNA genome, encapsulating it.
  9. The E proteins are moved to the golgi, and expressed on the PM.
  10. New virions bud.

Term
What makes Rubella unique to the other Toga viruses?
Definition

It is contracted through respiratory droplets, and causes no readily detectable cytopathological effects.

The main worry the cause of congenital cataracts in infected pregnant mothers.

Term

 

  1. Describe the pathogenesis of Rubella virus.
  2. In the fetus?

 

Definition

 

  1. It infects upper respiratory tract and spreads to lymph nodes (lymphadenopathy) followed by viremia. Infections of other tissue and mild rash result. 
  2. Virus not cytolytic. However normal growth, mitosis and chromosomal structure are altered in fetus producing teratogenic effects. 
Term
How is immunity acquired against Rubella?
Definition

Abs are generated after viremia, and its appearance correlates with the appearance of rash. Only one serotype, and lifelong immunity results. Immune complexes cause rash and arthralgia. 

Term
What is heterologous interaction?
Definition
In the case of rubella, the virus prevents the replication of superinfecting picornavirus.
Term
Epidemiology of Rubella.
Definition
Humans are the only host. The virus replicates in the pharynx, and the person is infectious as long as the virus is replicating.
Term
Clinical syndromes of Rubella
Definition

  1. Virus is normally benign in children. After a 14-21 day incubation period symptoms are a 3-day maculopapular or macular rash and swollen glands. 
  2. Infection in adults is more severe and includes arthralgia and arthritis and sometimes thrombocytopenia or postinfectious encephalopathy.
  3. Congenital disease in newborns is the chief concern = cataracts, retardation and deafness.

Term
Lab diagnosis of Rubella.
Definition

RT-PCR can be used to detect it.

IgM and a 4x increase in IgG titer are also indicative.

Term
Treatment for Rubella virus.
Definition

No treatment available.

Best option is to vaccinate w/ live cold-adapted RA27/3 vaccine strain (MMR) at 2yrs.

Only one serotype so eradication is possible.

Term
What does Varicella-Zoster Virus cause?
Definition

Chickenpox

Upon recurrence: shingles and herpes zoster.

Term
What do the alphherpesviridae have in common?
Definition

VZ and HSV are both members

Latent infection of neurons

Importance of cell-mediated immunity

Blister-like lesions

Like HSV, VZ produces thymidylate synthase, and is therefore susceptible to antiviral therapy.

Term

Where does the Varicella Zoster virus replicate?

How does it spread throughout the body>

Definition

VZ spreads and replicates in the respiratory tract.

Viremia after replication in the respiratory tract will lead to skin lesions (chickenpox etc).

Replicates slower and in fewer cells than HSV.

Unlike HSV, latently-infected cells produce a detectable protein.

Term
Pathogenesis of Varicella Zoster.
Definition
  1. Primary infection begins in tonsils and mucosa
  2. Spreads through blood and lymph to the reticuloendothelial system.
  3. 11-13 days later, a secondary viremia spreads the virus throughout entire body and skin.
  4. Virus overcomes IFN-a, and transmits from cell to cell, except for terminally-differentiated epithelial cells,
  5. Blister forms here, and is the infectious point
  6. In the event of recurrence, the virus will travel back down this neural pathway and present as herpes zoster or shingles
Term
Immunity to VZV
Definition

IFN-α is important to minimize the tissue spread of VZ, but Ab's are important in preventing viremic spread.

Passive immunization with VZ immune globulin (VZIG) is protective if done within 4 days of infection.

Adults have higher cell-mediated responses, therefore they have much worse reaction than children (especially in the lung).

Waning immune system is the reason for the recurrence of VZ late in life as shingles.

 

Term
Epidemiology of VZ
Definition

VZ can be passed through respiratory route or through direct contact.

Parents are contagious with or without symptoms.

This is a life-long disease.

Term
Lab diagnosis of VZ
Definition

Has similar CPEs to HSV (takes longer for them to show up with VZ)

Show Cowdry type A Bodies and syncytia.

Isolation of the virus is not done because it is labile in transport, and crusted-over skin tests negative.

Can use ELISA for serological analysis.

 

Term
What virus is Roseola infantum?
Definition

Human Herpes Virus 6 (HHV6)

Childhood disease is called exanthema subitum "Roseola" - caused by HHV6B or HHV7

 

Term
What is the Pathology of Roseola?
Definition

Infection occurs early in life.

Virus replicates in the salivary gland, and is shed and transmitted in saliva.

HHV6 like CMV, infects lymphocytes, monocytes, epithelial cells, and neurons. It establishes a latent infection in T cells and monocytes. Infected cells appear large and have inclusions.

Likely to become activated in AIDS patients. 

 

Term
Clinical Syndromes of Roseola
Definition

 

  1. Characterized by high fever of a few days followed by generalized rash that lasts 1-2 days. DTH (delayed-type hypersensitivity) cells in skin may be cause of rash. The disease is controlled by cell mediated immunity but there is a lifelong latent infection of T cells. 
  2. May cause a mononucleosis syndrome and lympadenopathy.
  3. Associated with multiple sclerosis and Chronic fatigue syndrome

 

Term

Divide the exanthematous viruses into:

 

DNA viruses

 

RNA viruses 

Definition
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