Holland: DNA Viruses Causing Respiratory Tract Infections Flashcards
Herpesviruses
General:
Over 100 herpesviruses known; 8 are considered human herpesviruses
Fall into 3 subfamilies based on genetic and biological properties
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
Betaherpesviruses: (4)
- CMV
- HHV-6A
- HHV-6B
- HHV-7
Gammaherpesviruses: (2)
- Epstein Barr Virus (EBV)
* HHV-8/Karposi’s sarcoma associated herpesvirus
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
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
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)
Epstein Barr Virus (EBV)
Transmission:
Site of primary infection:
o Transmission: saliva
o Site of primary infection: epithelial cells of upper respiratory tract
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
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)
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
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
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
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
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
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
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
Cytolomegalovirus (CMV)
Immunocompromised:
Neonatal and Fetal CMV:
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?
- Nonenveloped icosahedral
- Fibers at vertices (characteristic)
- Linear, dsDNA genome
- Replication in the nucleus
Adenoviruses
Host Cell Preference:
Mucosal epithelial cells: respiratory tract, small intestine, epithelial tissue of the eye
Adenoviruses
Portals of Entry: (3)
o Upper respiratory tract
o Alimentary canal
o Conjunctiva/cornea
Adenoviruses
Modes of Transmission: (3)
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:
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:
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
