Holland: DNA Viruses Causing Respiratory Tract Infections Flashcards by Andrew Kumar

Herpesviruses

General:

Over 100 herpesviruses known; 8 are considered human herpesviruses

Fall into 3 subfamilies based on genetic and biological properties

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Alphaherpesviruses: (3)

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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Betaherpesviruses: (4)

CMV
HHV-6A
HHV-6B
HHV-7

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Gammaherpesviruses: (2)

Epstein Barr Virus (EBV)

* HHV-8/Karposi’s sarcoma associated herpesvirus

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Epstein Barr Virus (EBV)

Primary Infection:

~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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Epstein Barr Virus (EBV)
Symptoms

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

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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Epstein Barr Virus (EBV)
Symptoms
Adolescents and Adults

Infectious mono:
Heterophile Abs:

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

o Transmission: saliva

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

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Epstein Barr Virus (EBV)

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

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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Epstein Barr Virus (EBV)
Spread to B lymphocytes

Lymphocytosis:
Potential for

Lymphocytosis (atypical lymphocytes)

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

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EBV and Cancer

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

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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EBV and Cancer
Nasopharyngeal Carcinoma (Southern China)

Epithelial cell cancer:
Viral genes expressed:
Possible cofactors:

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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EBV and Cancer

Hodgkin’s Lymphoma:
Viral genes expressed:

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

Sx:
B Cell Tumors:

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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EBV and Cancer

AIDS associated lymphomas:

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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Hairy Oral Leukoplakia:

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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Cytolomegalovirus (CMV)

Basics:
Symptoms:

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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Cytolomegalovirus (CMV)

Immunocompromised:
Neonatal and Fetal CMV:

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Immunocompromised: at risk for CMV pneumonia or retinitis

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

Adenoviruses

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

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

Adenoviruses

Host Cell Preference:

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

Adenoviruses

Portals of Entry: (3)

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o Upper respiratory tract
o Alimentary canal
o Conjunctiva/cornea

Adenoviruses

Modes of Transmission: (3)

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

Fecal/oral

Iatrogenic spread

Adenovirus Replication

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

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Receptor on Host Cell: CAR

Coreceptor on Host Cell: integrins

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

Adenovirus
Transcription/Translation
Early Proteins:

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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)

Adenovirus Transcription/Translation Late Proteins:

o Late Proteins: | • Virion structural proteins

Adenovirus | Virions released by:

- Virions released by cell lysis: inefficient, but a ton is made

Clinical Manifestations of Adenovirus Infections Acute Respiratory Infection ``` Acute febrile pharyngitis: Infectivity: IP: Age: Serotypes: ```

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)

Clinical Manifestations of Adenovirus Infections Acute Respiratory Disease (ARD): Common amongst: Severity ranges from ___ to ____ Live attenuated vaccines for:

- 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

Clinical Manifestations of Adenovirus Infections Pneumonia: Common cause of: Long-term complications more likely in:

Possible complication of any Adenovirus respiratory tract infection Common cause of childhood pneumonia and pneumonia in immunocompromise • Long-term complications more likely in children

Clinical Manifestations of Adenovirus Infections Pharyngoconjunctival Fever Components: Occurrence: Transmission:

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

Clinical Manifestations of Adenovirus Infections Epidemic Keratoconjunctivitis Involves:

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

Clinical Manifestations of Adenovirus Infections | GI Disease:

o Most replicate here but typically do not cause disease | o Types 40 and 41 associated with infant gastroenteritis (difficult to culture)

Clinical Manifestations of Adenovirus Infections | Urethritis/Cystitis:

o Uncommon forms of Adenovirus infection | o Type 27 associated with some cases of cervical lesions and make urethritis (sexual transmission)

Family: Parvoviridae | 2 Subfamilies:

o Parvovirinae Subfamily | o Dependovirinae Subfamily

Parvoviridae | Parvovirinae Subfamily:

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

Parvoviridae | Dependovirinae Subfamily:

* 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)

Parvoviridae Structure/Genome Size: Enveloped? Genome Where is replication?

- Small, noneveloped icosahedral - Linear, ssDNA genome (5 genes) - Nuclear replication

``` Parvovirus B19: Basics: Age: Prevalence: Transmission: ```

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

Erythema Infectiosum First Phase: Symptoms: Dispersion by: Shedding; Formation of:

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)

Erythema Infectiosum | Second Phase:

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

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

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

Transient Aplastic Crisis | Treatment:

Treatment: transfusion therapy

Parvovirus B19 in Immunocompromised Chronic infection of: Possible treatment with:

Chronic infection of the bone marrow, leading to persistent anemia Possible treatment with immune globulin

Congenital B19 Infections Can occur if: May cause: Congenital abnormalities in survivors:

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

Holland: DNA Viruses Causing Respiratory Tract Infections Flashcards

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