Holland: DNA Viruses Causing Respiratory Tract Infections Flashcards

1
Q

Herpesviruses

General:

A

Over 100 herpesviruses known; 8 are considered human herpesviruses

Fall into 3 subfamilies based on genetic and biological properties

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2
Q

Alphaherpesviruses: (3)

A
  • HSV 1
  • HSV 2
  • VZV
  • Note: B virus, a monkey alphaherpes virus, can infect humans (ie. via a bite); usually results in fatal encephalitis
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3
Q

Betaherpesviruses: (4)

A
  • CMV
  • HHV-6A
  • HHV-6B
  • HHV-7
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4
Q

Gammaherpesviruses: (2)

A
  • Epstein Barr Virus (EBV)

* HHV-8/Karposi’s sarcoma associated herpesvirus

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5
Q

Epstein Barr Virus (EBV)

Primary Infection:

A
  • ~50% children seropositive before age 5
  • Second wave of infection in adolescents and young adults
  • Socioeconomic conditions influence incidence and prevalence
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6
Q

Epstein Barr Virus (EBV)
Symptoms

Young Children:
If symptoms, most common are:
Less common:

A

Young Children: many primary infections asymptomatic

If symptoms, most common are: sore throat and fever

Less common: diarrhea, abdominal cramps, otitis media, infectious mono

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7
Q

Epstein Barr Virus (EBV)
Symptoms
Adolescents and Adults

Infectious mono:
Heterophile Abs:

A

Infectious mono: asymptomatic infections less common
- Fever, sore throat, nausea, anorexia, lymphadenopathy, splenomegaly, hepatomegaly, lymphocytosis, heterophile Abs

Heterophile Abs: Abs against unusual Ags, usually those which the person has never been exposed to (due to activation of B cells by EBV)

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8
Q

Epstein Barr Virus (EBV)
Transmission:
Site of primary infection:

A

o Transmission: saliva

o Site of primary infection: epithelial cells of upper respiratory tract

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9
Q

Epstein Barr Virus (EBV)

Spread to B lymphocytes:
What % infected?
Leads to secretion of:

A

Spread to B lymphocytes: lytic or latent infection of B cells
• Up to 10% may become infected (large number)
• Leads to secretion of heterophile Abs

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10
Q

Epstein Barr Virus (EBV)
Spread to B lymphocytes

Lymphocytosis:
Potential for

A
  • Lymphocytosis (atypical lymphocytes)

* Potential for subclinical virus shedding (some B cells latently infected after clearance)

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11
Q

EBV and Cancer

Burkitt’s Lymphoma (African Form):
Tumor cells:
Also have translocations of:
What may be a cofactor?

A

Burkitt’s Lymphoma (African Form): tumor of the jaw (childhood cancer)

Tumor cells are EBV+ B cells that express Epstein Barr Early RNAs (EBERs) and EBNA-1 (a viral protein)

Also have translocations of myc oncogene (overexpression)

Malaria infection may be a cofactor (excess replication of B cells)

Genetic predisposition possible

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12
Q
EBV and Cancer
Nasopharyngeal Carcinoma (Southern China)

Epithelial cell cancer:
Viral genes expressed:
Possible cofactors:

A

Epithelial cell cancer: tumor cells contain EBV DNA

Viral genes expressed: EBERs, EBNA-1, LMP-1, LMP-2

Possible cofactors: genetic, dietary and environmental

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13
Q

EBV and Cancer

Hodgkin’s Lymphoma:
Viral genes expressed:

A

o Hodgkin’s Lymphoma: EBV detected in ~50% of these cancers

• Viral genes expressed: EBERs, EBNA-1, LMP-1, LMP-2

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14
Q

EBV and Cancer
Cancers in immunocompromised
Post-transplant lymphoproliferative disorders and lymphomas

Sx:
B Cell Tumors:

A

Post-transplant lymphoproliferative disorders and lymphomas:

  • Sx: B cell proliferation, sore throat, fever
  • B Cell Tumors: tend to be aggressive and difficult to treat
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15
Q

EBV and Cancer

AIDS associated lymphomas:

A

AIDS associated lymphomas: increased incidence (50-100 fold) over general population

  • Tend to occur in CNS
  • Late manifestation of HIV-1 infection
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16
Q

Hairy Oral Leukoplakia:

A

EBV infection occurring in the mouth of AIDS patients

  • White, wart like lesions on sides of tongue (sites of active EBV replication)
  • Not a tumor
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17
Q

Cytolomegalovirus (CMV)

Basics:
Symptoms:

A

Basics: very common infection
o Viruses shed in urine, saliva, and other bodily fluids (can persist for months)

Symptoms: usually asymptomatic
o May cause an infectious mono-like disease (heterophile Ab negative)
o Enlarged spleen or liver

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18
Q

Cytolomegalovirus (CMV)

Immunocompromised:
Neonatal and Fetal CMV:

A

Immunocompromised: at risk for CMV pneumonia or retinitis

Neonatal and Fetal CMV: major problem (risk of death, mental retardation, deafness)

19
Q

Adenoviruses

Enveloped?
What’s at vertices?
Genome:
Where is replication?

A
  • Nonenveloped icosahedral
  • Fibers at vertices (characteristic)
  • Linear, dsDNA genome
  • Replication in the nucleus
20
Q

Adenoviruses

Host Cell Preference:

A

Mucosal epithelial cells: respiratory tract, small intestine, epithelial tissue of the eye

21
Q

Adenoviruses

Portals of Entry: (3)

A

o Upper respiratory tract
o Alimentary canal
o Conjunctiva/cornea

22
Q

Adenoviruses

Modes of Transmission: (3)

A
Respiratory spread (most common)
•	Even in this type of transmission, adenovirus spreads to intestinal tract and is spread in feces

Fecal/oral

Iatrogenic spread

23
Q

Adenovirus Replication

Receptor on Host Cell:
Coreceptor on Host Cell:
Entry:

A

Receptor on Host Cell: CAR

Coreceptor on Host Cell: integrins

Entry: endocytosis; capsid transported to nuclear pore and DNA released into the nucleus

24
Q

Adenovirus
Transcription/Translation
Early Proteins:

A
Early Proteins:
•	Alter cell cycle
•	Block apoptosis
•	Replicate viral DNA
•	Block CTL responses by inhibiting MHC class I (they can’t recognize the infected cell)
25
Q

Adenovirus
Transcription/Translation
Late Proteins:

A

o Late Proteins:

• Virion structural proteins

26
Q

Adenovirus

Virions released by:

A
  • Virions released by cell lysis: inefficient, but a ton is made
27
Q

Clinical Manifestations of Adenovirus Infections
Acute Respiratory Infection

Acute febrile pharyngitis: 
Infectivity:
IP:
Age:
Serotypes:
A

Acute febrile pharyngitis: fever, sore throat, cough, nasal congestion, possibly tonsillitis
• Highly infections
• 5-8 day incubation period
• Typically during childhood
• Several common serotypes (little or no cross-immunity between them)

28
Q

Clinical Manifestations of Adenovirus Infections

Acute Respiratory Disease (ARD):
Common amongst:
Severity ranges from ___ to ____
Live attenuated vaccines for:

A
  • Acute Respiratory Disease (ARD):
    o Common amongst military recruits (easily spread due to crowded living conditions and stress)
    o Severity ranges from mild upper respiratory infection to pneumonia
    o Live attenuated vaccines for military use only
29
Q

Clinical Manifestations of Adenovirus Infections

Pneumonia:

Common cause of:
Long-term complications more likely in:

A

Possible complication of any Adenovirus respiratory tract infection

Common cause of childhood pneumonia and pneumonia in immunocompromise
• Long-term complications more likely in children

30
Q

Clinical Manifestations of Adenovirus Infections

Pharyngoconjunctival Fever

Components:
Occurrence:
Transmission:

A

Components:
• Conjuntivitis (Pink Eye): redness, watering, discomfort, photophobia
• Upper Respiratory Tract Infection: fever, sore throat, cough, nasal congestion

Occurrence: tend to be sporadic and localized outbreaks

Transmission: upper respiratory droplets, fomites, swimming pools

31
Q

Clinical Manifestations of Adenovirus Infections
Epidemic Keratoconjunctivitis

Involves:

A

Involves both cornea and conjunctiva:
• High contagious
• May result in permanent corneal damage and degradation of vision
• Usually requires minor corneal abrasions
• Has been associated with iatrogenic spread

32
Q

Clinical Manifestations of Adenovirus Infections

GI Disease:

A

o Most replicate here but typically do not cause disease

o Types 40 and 41 associated with infant gastroenteritis (difficult to culture)

33
Q

Clinical Manifestations of Adenovirus Infections

Urethritis/Cystitis:

A

o Uncommon forms of Adenovirus infection

o Type 27 associated with some cases of cervical lesions and make urethritis (sexual transmission)

34
Q

Family: Parvoviridae

2 Subfamilies:

A

o Parvovirinae Subfamily

o Dependovirinae Subfamily

35
Q

Parvoviridae

Parvovirinae Subfamily:

A

• Autonomously replicating
• Only Parvovirus B19 confirmed to cause infection in humans (some newer ones suspected)
➢ Human bocavirus (GI/RT disease?)
➢ PARV4 (unclear)

36
Q

Parvoviridae

Dependovirinae Subfamily:

A
  • Adeno-associated viruses types 1-5
  • Require helper viruses (Adenoviruses, Herpesviruses)
  • Not known to be associated with any human disease (being researched as possible gene therapy vectors)
37
Q

Parvoviridae
Structure/Genome

Size:
Enveloped?
Genome
Where is replication?

A
  • Small, noneveloped icosahedral
  • Linear, ssDNA genome (5 genes)
  • Nuclear replication
38
Q
Parvovirus B19:
Basics: 
Age:
Prevalence:
Transmission:
A

Basics: causes Erythema Infectiosum (Fifth Disease), but many infections are asymptomatic
o Typically in school age children
o Prevalence of Abs to B19 increases with age
o Transmission is probably by respiratory route

39
Q

Erythema Infectiosum
First Phase:

Symptoms:
Dispersion by:
Shedding;
Formation of:

A

First Phase:
• Non-specific flu like symptoms (fevers, chills, malaise, myalgia, itching)
• Dispersion of virus by viremia
• Shedding of virus from upper respiratory tract
• Formation of IgM-parvovirus immune complexes (which give rise to second phase of disease)

40
Q

Erythema Infectiosum

Second Phase:

A

Second Phase: deposition of immune complexes leading to erythematous rash and arthritis

41
Q
Parvovirus B19
Transient Aplastic Crisis
Can be seen in what patient population?
Where does B19 replicate?
Causes:
In normal individuals:
A

Can be seen in B19 infection in people with hemolytic anemia: ie. sickle cell disease

B19 replicates in bone marrow, specifically in erythroid precursor cells

  • Causes profound transient reduction in erythrocyte production
  • Not a major problem in normal individuals, but can be life-threatening in patients with pre-existing hemolytic anemia
42
Q

Transient Aplastic Crisis

Treatment:

A

Treatment: transfusion therapy

43
Q

Parvovirus B19 in Immunocompromised

Chronic infection of:
Possible treatment with:

A

Chronic infection of the bone marrow, leading to persistent anemia

Possible treatment with immune globulin

44
Q

Congenital B19 Infections

Can occur if:
May cause:
Congenital abnormalities in survivors:

A

Can occur if primary B19 infection of pregnant woman

May cause hydrops fetals (fatal anemia of the fetus)

No evidence of congenital abnormalities in survivors