Viral Upper Respiratory Infections Flashcards
(24 cards)
Rhinovirus structure
Non-enveloped
+ssRNA genome (7-8kb)
Icosahedral capsid
Small in size (~30 nm)
Rhinovirus biological characteristics
> 100 serotypes
- ICAM-1 is the primary cellular receptor used to infect respiratory epithelial cells
- Temperature sensitive: Grows and replicates more efficiently at 88-90 degrees F (the temperature in the nose) than at 98 degrees F (the temperature in the lungs)
- Acid labile: destroyed by GI tract
Rhinovirus life cycle
- Enters host cell via ICAM-1
- Translation of coat proteins and replication of RNA
- Encodes its own RNA polymerase
- Assembly and exit by lysis
Rhinovirus Pathogenesis, Symptoms, and complications
-Pathogenesis and Symptoms
-Infection lasts about two to four days and self-limiting
-Inflammatory responses caused by rhinovirus leads to:
Nasal discharge
Nasal congestion
Sneezing
Sore throat
Edema and erythema of nasal mucosa
Muscle aches, fatigue, headache, loss of appetite
-Complications:
-rare cases: bronchopenumonia in young children
Rhinovirus: Diagnosis, Prevention, Vaccine, Treatment
- Diagnosis: Clinical presentation
- Preventive Measures:
- Sanitation and hygiene helps prevent spread
- Mucosal IgA in nasal secretions are protective
- Type I INF control viral spread but causes pathogenesis
- Vaccination
- Immunity is serotype specific but there are currently no vaccines due to >100 serotypes
- Treatment: Based on symptoms
- Treatment is primarily symptomatic
Respiratory Syncytial Virus: (Paramyxovirus family) Structure
- Enveloped
- negative ssRNA genome
- Helical capsid
- 100 – 300 nm
- Two major envelope proteins
- F = fusion protein
- Cause respiratory epithelium to fuse
- Form mononucleated cells
- G = attachment protein
- Encodes its own RNA-dependent-RNA Polymerase
Respiratory Syncytial Virus: (Paramyxovirus family): Biological Characteristics
-Transmitted by aerosol droplets and direct contact with contaminated surfaces
-Nosocomial spread is common
-Disease can be severe in immunocompromised people
-Target Cells:
-epithelial cells of URT
-Produces mild illness that is self-limiting.
~50% children <8 months, virus spreads into the LRT causing bronchitis, pneumonia and croup
Respiratory Syncytial Virus: (Paramyxovirus family): Life Cycle
- negative ssRNA replicates cytoplasmically
- Assembled RNA and protein binds glycoproteins and gets exocytosed
- Forms syncytium with all the parts
Respiratory Syncytial Virus: (Paramyxovirus family): Pathogenesis, Symptoms, and Complications
Pathogenesis and Symptoms:
-Infection is self-limiting and lasts a week to 10 days
-Runny nose, Fever, Rapid breathing, Continuous coughing
-Wheezing and/or a loud whistling sound while exhaling and breathlessness
-Contraction of abdominal muscles while breathing
-Lips turn blue
-Infection induces protective immunity that is not long lasting leading to repeat infections
-premature infants t fully develop
Complications:
-Disease can be severe in immunocompromised people
Respiratory Syncytial Virus: (Paramyxovirus family): Diagnosis
- Nasal washings, nasal aspirates or swab samples are useful for antigen detection
- Rapid diagnosis is carried out using DFA, IFA, ELISA.
- Viral culture carried out in cell lines such as HeLa, Hep-2, Monkey Kidney cells.
- CPE is seen in 2-5 days
- Molecular assays such as RT-PCR
Respiratory Syncytial Virus: (Paramyxovirus family): Treatment
-Ribavirin has been used. efficacy has been found to be limited
-O2 treatment & hospitalization for infants w/ severe bronchiolitis
Passive Immunotherapy:
-RespiGam: polyclonal antibody used to prevent serious lower respiratory tract infection by RSV.
-Infants and bone marrow recipients.
-Synagis®(palivizumab): 1st monoclonal antibody successfully developed.
-Anti-F reactive antibody.
-Indicated for the prevention of serious lower respiratory tract disease caused by RSV in pediatric patients at high-risk
Safety and efficacy were established in infants with broncho-pulmonary dysplasia (BPD) and infants with a history of prematurity
-No vaccine available
Adenovirus: Structure
- Non-enveloped
- ds linear DNA genome, 36 kbps
- Icosahedral capsid
- Largest non-enveloped virus (70-90 nm)
Adenovirus: Biological Characteristics:
- At least 51 serotypes are known
- Replicates in the nucleus
- Ubiqiutus DNA virus
- Immunity is serospecific
- Transmission is by direct contact
- Target Cells: Infects mucoepithelial cells in respiratory tract, GI-tract, and conjunctiva or cornea
Adenovirus: Life Cycle
- Binds CAR (Coxsackievirus and Adenovirus receptor) and is taken into the cell
- In the endosome it makes microtubules to reach the nucleus
- Encodes it own DNA polymerase: copies the DNA in the nucleus
- Virus persists in lymphoid tissues (tonsils, adenoids, Peyer’s patches) and kidney.
Adenovirus: Pathogenesis and Symptoms
- Causes 5-10% of febrile illness in early childhood
- Transmission is by direct contact
- Fecal-oral, contaminated water, objects, Aerosol droplets
- Clinical manifestation varies with the age and immune status of the host
- Immunity is serotype specific
- Pharyngoconjuctival fever in crowded places such as summer camps, swimming pools – Ad3, 7
- Conjunctivitis
- Acute respiratory disease in military recruits – Ad4, 7
- Febrile, undifferentiated upper respiratory tract infection: Infants, young children (5-10% of cases)
- Febrile pharyngitis
- Sore throat, acute hemorrhagic cystitis
- Pharyngoconjunctival fever (Ad3, 5, 7, 21): Children, adults
- Acute respiratory disease (Ad4 and Ad7): Military recruits
- Pertussis-like syndrome: infants, young children
- Pneumonia
Adenovirus: Immunity
- Humoral
- Neutralizing antibodies protective against same serotype
- age 10: most have antibodies against endemic serotypes
- Cell Mediated
- CD8 CTL responses are critical in controlling infection
- Severe infections common if cellular immune defects
- Encodes proteins that play a role in immune evasion
- (For ex: E3 protein)
- down regulates MHC class I
- inhibit TNF mediated lysis
Adenovirus: Diagnosis
- Detection of Antigen
- A rapid diagnosis from nasopharyngeal aspirates and throat washings
- Virus Isolation from nasopharyngeal aspirates, throat swabs, and feces
- Retrospective diagnosis may be made by serology. Complement -Fixation Test most widely used.
- PCR assays
Adenovirus: Treatment
- Symptomatic
- Sanitation and hygiene can limit spread
- Disease resolves in 7-10 days
- Live Ad4 and 7 vaccines used in military but discontinued in 1999 after stopped production
- New live tablet vaccine (99.3% protection again Ad4 & 7) approved in 2011 for use by the US Military during basic training across the various training sites in the US
Epstein Barr virus: Structure
- All Herpesviruses have identical morphology
- Enveloped
- Large genome (~80-100 genes)
- Linear dsDNA
- Icosahedral capsid
Epstein Barr Virus: Biological Characteristics
- g - Herpesviruses : EBV, KSHV/HHV-8
- restricted host-range
- latent in lymphocytes and/or endothelial cells
- Ubiquitous
- Transmission primarily oral route and virus is shed in the saliva
- Incubation period lasts about 6-8 weeks with symptoms persisting for 2-3 weeks
- Target Cells: infect epithelial cells and lymphocytes
Epstein Barr Virus: Life Cycle
- Encodes its own DNA-Dependent-DNA Polymerase
- Encodes numerous host protein homologues to evade immune responses
- Replicates inside the nucleus
- Mature virus processed thru ER and golgi and released as mature product
Epstein Barr Virus
- adolescents are a major risk group with 35-50% of infections leading to infectious mononucleosis (kissing disease; Glandular fever)
- Transmission primarily oral route and virus is shed in the saliva
- Incubation period lasts about 6-8 weeks with symptoms persisting for 2-3 weeks
- Virus infects and replicates in epithelial and B cells
- Tonsils: red, swollen, and white patches
- Throat: red and sore
- Central: malaise, fatigue, headache, loss of appetite
- Visual: photophobia
- Lymph node: swelling
- Spleen enlargement and abdominal pain
- Complications:
- Hodgkin’s and Burkitt’s Lympphoma
- Nasopharyngeal carcinoma
Epstein Barr Virus:
- Atypical lymphocyte: downty cell: CD8+ CTL
- Agglutination test for heterophile antibodies: Positive monospot test
- EBV antibody ELISA
- PCR for EBV genes
Epstein Barr Virus: Treatment
Symptomatic
IM is self limiting and rapidly controlled by the immune response
No licensed vaccine yet
