Orthomyxovirus and Paramyxovirus Flashcards
o Contain seven segments of RNA
o Lacks a neuraminidase gene
Influenza C
- Virus-encoded glycoproteins
- Inserted into the lipid envelope
- Determine antigenic variation and host immunity
HA and NA
- Protein in viral envelope - Used as an attachment/entry receptor - Binds to N-acetylneuraminic acid on the host cell glycolipids or glycoproteins - Hemagglutinin hydrolysed by host cell proteases to created infectious virion
HA
Functions at the end of the viral replication cycle
NA
Facilitates release of virus particles from infected cell surfaces during budding
NA
Helps the virus negotiate thought the mucin layer in the respiratory tract to reach the target epithelial cells
NA
- Antigenically highly variable
- Responsible for most cases of epidemic influenza
- Also know for some animals (birds, pugs, horses, and seals)
Influenza A
May exhibit antigenic changes
- Can sometimes cause epidemics
Influenza B
- Antigenically stable
- Cause on mild illness in immunocompetent individuals
Influenza C
Segmented nature of the genome
GENETIC REASSORTMENT
Result in hidden changes in viral surface antigens
GENETIC REASSORTMENT
interval between epidemic waves of influenza A
Every 2-3 years
a new subtype of influenza A appears and a pandemic may result
Every 10-40 years
- Early 2009
- Novel swine-origin H1N1 virus
- Pandemic spread by mid-year
- Was a quadruple reassortment
- 18,000 deaths
- Has become a seasonal influenza virus
A (H1N1)
Reflects drastic changes in the sequences of viral surface protein, cause by genetic reassortment between human, swine, avian influenza viruses
Antigenic Shift
- Most likely to result in an epidemic
- Gives rise to pandemics of influenza A
- Seasonal influenza
Antigenic Shift
- minor antigenic changes
- caused by the accumulation of point mutations in the genes
- resulting in amino acid changes in the protein a variant must sustain two of more mutations before a new, epidemiologically significant strain emerges
- causes yearly epidemics
- pandemic influenza
- sequence changes can alter antigenic sites on the molecule such that a virion can escape recognition by the host’s immune system
Antigenic drift
alter antigenic sites on the molecule such that a virion can escape recognition by the host’s immune system
Sequence changes
Incubation period of Influenza virus
1-4 days
MOT of Influenza Virus
person to person by airborne droplets or contact with contaminated hands or surfaces
Viral shedding of the Influenza virus.
Peaks within _______
24hrs
Influenza virus remain elevated for
1-2 days
Declines over the next _____
5 days
What are the immune defense against Influenza virus?
o Cough reflex
o Neutralization by preexisting specific immunoglobulin A (IgA) antibodies
o Inactivation by non-specific inhibitors in the mucous secretions
lowers viscosity of mucous film in respiratory tract
o Lays bare the cellular surface receptors
o Promotes the spread of virus-containing fluid to lower portions of the tract
Viral Neuraminidase
cause cellular destruction of the superficial mucosa of the respiratory tract
o Do not affect basal layer of epithelium
o Lowers its resistance to secondary bacterial pathogen
Influenza infection
detectable respiratory secretions 1 day after viral shedding begins
Interferon
Wha are the Local symptoms of Inluenza virus?
Edema and PMN infiltration
Wha are the fever and systemic symptoms of influenza virus?
Action of cytokines
It causes Chills, headache, dry cough followed closely by high fever, generalized muscular aches, malaise, and anorexia.
Uncomplicated influenza
Fever in uncomplicated influenza lasts for _______
3-5 days
Respiratory Sx of uncomplicated influenza lasts another ______
3-4 days
Cough and weakness of uncomplicated influenza may persist for ________
2-4 weeks
similar to those in adults although children may have higher fever and a higher incidence of GI manifestations such as vomiting + febrile seizures may occur
Uncomplicated influenza in children
Important cause if croup
Influenza A virus
Serious complications occur only in elderly adults and debilitated individuals, especially those with underlying chronic disease
Pneumonia
Attributed to loss of ciliary clearance, dysfunction of phagocytic cells, and provision of a rich bacterial growth medium by alveolar exudate
Pneumonia
What are the bacterial pathogen of Penumonia
S. Aureus
Step pneumonia
H. Influenza
It is an An acute encephalopathy of children and adolescents )2-16 years old)
Reye syndrome
Mortality rate of Reye Syndrome
10-40%
Persists for months or years in regards to protecion correlates of Influenza virus
Serum antibodies
- Individual develops antibodies to flu antigens after first exposure
- On 2nd exposure antigens changed inducing a new array of antibodies
- When a viral type undergoes antigenic drift, a person with preexisting antibody to the original strain may have only mild infection with the new strain
Original Antigenic Sin
In regards to the Lab diagnosis of Influenza virus, Specimens should be obtained within ______ after the onset of symptoms
3 days
What are the 3 specimens obtained for the lab diagnosis of influenza virus?
o Nasopharyngeal swabs o Nasal aspirate o Lavage fluid
identification of viral antigens or viral nucleic acid
▪ Preferred
▪ Rapid (<1 day) sensitive and specific
RT PCR
isolation of the virus of the Influnza virus
Cell structure
demonstration of a specific immunologic response
Serology
When should Drugs must be administered in the disease to be maximally effective?
Very early in the diasease
- M2 ion channel inhibitors
– blocks viral uncoating
-Treatment and prophylaxis of influenza A
Amantidine hydrochloride and rimantadine (analog)
- NA inhibitors - Useful treatment for both influenza A and B
Zanamivir, oseltamivir, and peramivir
Do inactive viral vaccines generate good local IgA or cell-mediated immune responses
NO!
Contraindication of vaccines for Influenza virus
History of allergy to egg protein
Annual influenza vaccination is recommended for:
o All children ages ________
6 months to 18 years
High risk groups in vaccination to influenza virus
▪ Chronic hear of lunch disease (asthma)
▪ Metabolic or renal disorders
▪ Resident nursing homes
▪ Persons infected with the human immunodeficiency virus
▪ 65 years of age and older
All member initiate infection via the respiratory tract
Paramyxoviruses
Respiratory pathogens: replication is limited to the respiratory epithelia
Respiratory syncytial virus (RSV)
Para influenza virus
Disseminated causing generalized disease
Mumps and measles virus
- Spherical, pleomorphic, with helical nucleocapsid
- Single-stranded, linear, RNA genome, non-segmented, negative sense
Paramyxoviruses
mediates membrane fusion and hemolysin activity; causes fusion of adjacent cell membranes resulting in formation of large syncytia
F glycoprotein
Replicate in the cytoplasm of the host cell, particles bud from the plasma membrane of the host cell
Paramyxoviruses
MOT of Parainfluenza viruses
direct person to person contact and large droplet aerosols
IP of PIV
5-6 days
What causes LTB (Croup)?
PIV Type 1 and 2
LTB occurs in children _______
6-18 months
Presents with stridor and a barking cough (like a seal) occur due to narrowed airways
PIV
What causes Bronchiolitis and Pneumonia?
PIV Type 3
Most common complication of Pneumonia and Bronchiolitis
Otitis media
What happen to patients with immunocompromised affectedcwith PIV?
Severe infection
PIV shedding is about _______ after the onset of illness
1 week
Some children may excrete virus several days _____ to illness
Prior
may be excreted for up to 4 weeks after onset of primary infection
Type 3
Type 3- may be excreted for up to ______ after onset of primary infection
4 weeks
Most prevalent; 2/4 of infants are infected during the 1st year of life, all have antibodies at age 2
Type 3 PIV
most important protection against reinfection (disappear within a few months)
Secretory IgA
In the Lab diagnosis of PIV RT PCR is used to ______.
Nucleic acid detection test
In lab diagnosis of PIV, this is used to detect antigens in exfoliated nasopharyngeal cells – rapid but less sensitive
Direct and indirect immunofluorescence test
In lab diagnosis of PIV, the use of _______ is continuous for the isolation of virus.
monkey kidney cell line LLC-MK2
a. Based on paired sera
b. a four-fold rise in titer is indicative of infection (ELISA, neutralization, HI tests)
Serology
for treatment of immunocompromised patients with lower respiratory tract disease
Ribavirin
Prevention of PIV
- isolation of infected patients - gowning and hand-washing by medical personnel - no vaccine available
- does not have a hemagglutinin
- the most common cause of bronchiolitis and pneumonia in infants under 1 year of age
Respiratory Syncytial Virus
IP of RSV
3-5 days
In viral shedding of RSV,
o Persists for _______ in infants and young children
o While adults shed only for ________
Children: 1-3 weeks
Adult: 1-2 days
important determination of successful infection in RSV
Inoculum size
Although the virus is very labile, it can survive on environmental surfaces for up to 6 hours
RSV
Main portal of entry of RSV
Eyes and nose
MOT of RSV Infection
large droplet and direct contact
most important cause of viral pneumonia in infants and young children
RSV
Its clinical maninfestation includes: Common cold Pneumonia Bronchiolitis Otitis Media
RSV
Does RSV an effective inducer of interferon?
No
important in recovery from infection of RSV
Cellular immunity
have been correlated with occurrence of bronchiolitis
Viral secretory IgE antibodies
Most sensitive for viral isolation of RSV
HeLa and HEp-2
How to treat patients with RSV
Supportive removal of secretions and oxygen administration
Given in infants with lower respiratory tract at high rish for severe disease
Ribavirin
Ribavirin is Administered in an aerosol for _________
3-6 days
A respiratory pathogen described in 2001
HUMAN METAPNEUMOVIRUS
Infection occurs in all age groups, but especially in pediatric patients
HUMAN METAPNEUMOVIRUS
IP of Human Metapnuemovirus
4-9 days
In shedding of Human Metapneumivirus.
Children: _____
Immunocompromised: _______
5 days
Several weeks
method of choice for Lab diagnosis of Human metapneumovirus
RT-PCR Assay
Treatment for human metapneumovirus
No specific therapy and no vaccine available
Only known natural host of mumps virus infection
Human
IP of mumps
14-18 days
Primary replication occurs in __________ → circulation → salivary glands and other organs (kidneys and CNS)
nasal or URT epithelial cells
Viral shedding in saliva in mumps
3 days before to 9 days after the onset of salivary gland swelling
▪ Appear 3-7 days after onset of clinical syptoms
▪ Disappear within 6 months
Nucleocapsid protein
Develop ~4 weeks and persist for years
HN glycoprotein
Passive immunity from mother to offspring
Cell-mediated immune response also develops
Immunity of mumps
Nucleic acid detection in mumps infection
RT-PCR assay
This is used for the Isolation and identification of the virus
saliva, CSF, urine (up to 2 weeks)
Mumos infection is Highest incidence in ________
children aged 5-9 yrs
MOT of mumps infection
direct contact, airborne droplets, or fomites contaminated by saliva or urine
Treatment and prevention of mumps infection
No specific therapy
Vaccine of mumps virus
attenuated live mump virus (MMR)
Receptor of Measles
CD 46 or CD 150
IP of Rubeola
8-15 days
3 weeks in children
MOT of Rubeola
inhalation of large droplets on infected secretions → respiratory tract → regional LN → blood → RES → blood → skin, RT, conjunctiva
In Rubeola, Multinucleated giant cells with intranuclear inclusions are seen in lymphoid tissues throughout the body
Warthin-finkeldey cells)
pathognomonic for measles; small, bluish-white ulcerations on the buccal mucosa opposite the lower molars that appear two days before the rash
Koplik’s spot
In phases of Measles, maculo-papular rash spreading cephalocaudally; results to brownish desquamation in 5-10 days; px is contagious during the prodromal phase and the first 2-5 days of rash
Eruptive stage
Most common complication of rubeola
Otitis media
most common life-threatening of rubeola
Pneumonia
most serious complication of Rubeola
Acute-encephalitis
Progressive mental deterioration, involuntary movements, muscular rigidity and come
Subacute sclerosing panencephalitis
When is SSPE usually fatal?
Within 1-3 years after onset
- Highly contagious
- A single serotype
- No animal reservoir
- Inapparent infections are rare
- Infections confer lifelong immunity
Rubeola/Measles
Cause of encephalitis outbreaks in Australia and in Malaysia
Hendra and Nipah virus
▪ from pigs to humans
▪ cause severe encephalitis
▪ associated high mortality rate
Nipah virus
▪ equine – humans
▪ equine virus
▪ also causes encephalitis
▪ results to high mortality rate
Hendra virus
Natural host for Hendra and Nipa virus
Fruit bats
No vaccine, no proven therapies available
Henipavirus
Large, enveloped viruses with widely-spaced club or petal shaped spikes (S glycoprotein)
- Spherical virion with helical nucleocapsid
- Single-stranded, linear RNA genome-non-segmented, positive sense
Coronavirus
Contain another glycoprotein, hemagglutinin esterase (HE)
Human coronavirus OC43 (HCoV-OC43)
Replicate in the cytoplasm of the host cell, particles mature by budding into the ER and Golgi apparatus
Human coronavirus OC43 (HCoV-OC43)
What are the Six coronaviruses that infect humans?
o Alpha coronaviruses 229E
NL63
o Beta coronaviruses OC43, HKU1
o SARS-CoV o MERS-CoV
Exhibit a high frequency of mutation and recombination during replication
Coronavirus
Difficult to grow in cell culture
Coronavirus
In humans, usually limited to infections of respiratory tract
Coronavirus
MOT Of Coronavirus
o airborne (close contacts) o fomites: frequently touched surfaces
This occurs in in adults (15-30% of all colds) of patients with coronoviruse
Common colds
IP of coronavirus
2-5 days, Sx lasting for 1 week without fever
Severe Acute Respiratory Syndrome: pneumonia and progressive respiratory failure
SARS
IP of SARS
6 days
Its symptoms are fever, malaise, chills, headache, dizziness, cough, and sore throat
SARS
Its symptoms in the long run are the: shortness of breath – may rapidly progress of acute respiratory distress
SARS
o Pneumonia and progressive respiratory failure
o Most px who died had medical comorbidities
o Likely originated in bats and camels
MERS-COV (2012)
Used to detect coronavirus antigens in cells in respiratory secretions in patients with SARS
ELISA Test
to detect coronavirus nucleic acid in respiratory secretions and in stool, and plasma – between day 4 and 8 infection
PCR
Difficult to culture; however, SARS virus was recovered from oropharyngeal specimens using _________
Vero monkey kidney cells
How to prevent patients with SARS?
- Isolation of patients
- Quarantine of those who have been exposed
- Travel restrictions
- Use of gloves, gowns, goggles, and respirators by health care workers
