orthomyxoviruses Flashcards
what are orthomyxoviruses?
are a family of RNA viruses that includes seven genera: Influenza virus A, Influenza virus B, Influenza virus C, Influenza virus D, Isavirus, Thogotovirus and Quaranjavirus.
influenza ABC are major determinant of morbidity and mortality caused by respiratory disease
myxo
mucus
three types of influenza virus
influenza A, B, C
structural composition of influenza
spherical shape
ss -ve sense RNA genome
types A,B - 8 segmented genome
type C- 7 segmented genome
9 different structural proteins
what are the 9 proteins of influenza?
- ribonucleoprotein (RNP)
- PB1,2, PA- bind to the RNP, responsible for
transcription and replication - Matrix (m1) protein- form a shell below the viral envelope
- lipid envelop- derived from cell
- glycoprotein- (hemagglutinin (HA))
(neuraminidase (NA)) - M2 ion channel protein
- non structural protein (NP)
function of HA?
attach virus to cell surface receptor
function of NA?
used to release the virus from infected cell surface
it help to prevent self aggregation of viruses during viral release
what determines the antigenic variations of the virus
HA AND NA
minor antigenic changes
antigenic draft
major antigenic changes
antigenic shift
based on antigenic diff the virus is divided into ?
influenza A,B,C
influenza A
antigenic ally variably high
responsible for most cases of epidemic influenza in human
also causes disease in aquatic birds, horses and pigs
influenza B
may exhibit antigenic change
some times causes epidemic in human only
INFLUENZA C
antigenic ally stable
causes inf in swine and human
physiochemical character of influenza
withstands room temp
withstands dust
resistant at alkaline PH
destroyed by lipid solvent - phenol, ethanol, ether, formaldehyde
destroyed by uv rays and gamma rays
viral attachment, penetration and uncoating of influenza?
attaches to cell surface sialic acid by HA
penetrate within endosome by endocytosis
uncoat by fusion of the viral envelop with the endosome cell membrane
viral replication of influenza
transcription and replication occurs in the nucleus
shuts down the host cell protien synthesis 3hrs after inf
new virus is produced within 8-10 hrs
-ve ss RNA forms +ve strand
then RNA replication starts
nucleiocapsids are assembled in the nucleus
virus moves out to the cell surface
the HA,NA are synthesized in the endoplasmic reticulum
HA, NA are inserted in the plasma membrane
the insertion is with the help of M1
viruses are released by budding
NA removes the salic acid from cellular surface gp
pathogenesis of influenza
spread from person to person
inhaled virus is deposited on mucous of the respiratory tract or in the alveoli
incubation period- 18-72 hrs
the virus changes the ciliated columnar epithelial cell of the RT into round, swollen, nucleus shinks- pyknotic and fragment, vacolulization of the cytoplasm
cytoplasm shows inclusion bodies and the cilia are lost
release of virus allow it to spread to other cells in respiratory area
cell damage initiates acute IR with edema and phagocytic cells
1. release of interferons- protect viral spread
2. t cells- cytotoxicity damages the epithelium and lead to
3. secondary inf- strap, strept, h.influenza
4. URT and LRT inf- causes dry cough
- main physical findings is pyrexia ( peak of 38-41oc within 12hrs)
- Fever usually last after 3 days
- during the 2nd and 3rd day of the illness the systemic effect disappear
- at the 4th day, respiratory symptoms are high with laryngitis, pharyngitis, tracheobronchitits
- in adult system illness without respiratory symptoms is common
viral spread start during onset of symptoms and peak within 24hrs then reduce over the next 5 days - viremia is rare
clinical features of influenza A
incubation period is short- 2days (vary fro 1-4)
the illness is chills, fever, headache, myalgia, anorexia, rhinitis, cough,ocular symptoms
1/3 of the patient will suffer from common cold
clinical features of influenza B
symptoms resembles that of influenza A but milder
show more involvement of the go tract- gastric flu
clinical features of influenza C
afebrile URT inf, usually occur in young children
complication of influenza
1.primary influenza pneumonia-young adult/old people
can be fatal after a very short day
2. a bacterial pneumonia(s.aureus/ s. pneumonia) with biphasic fever
3. chest pain in old people
4. severe inf/sudden death occur in patient with
cerebrovascular disease
cardiovascular disease
chronic respiratory disease
5. disease in pregnancy- schizophrenia
lab diagnosis
virus isolation-monkey kidney
baboon kidney
human embryonic kidney cells
presence of virus may be detected after 18hrs by hemmaglutination with human o gp or gurineapig roc
rapid diagnosis-bnasal aspirate, nasal wash
PCR
treatment of influenza
oral amantadine HCL
rimantadine
They block the ion channel in the envelope and cell membrane during viral fusion
prevention
rimantadine- M2- type A only
amantidine-M2- type A only
ZANAMIVIR-NA- type A and B but not yet approved
OSELTAMIVIR-NA- type A and B
WHO recommendation
embryonate eggs cultivated viral vaccine- whole virus, subunit viral particle, surface antigen
annual influenza vaccine- for increased risk pple chronic heart/lungs disease asthma renal disorder hospital workers older persons with influenza virus
Epidemiology of influenza
occurs worldwide type A causes pandemics all three go try antigenic drift only A goes thru antigenic shift A is isolated from- ducks, chickens, turkeys, geese, pigs and horses
where do new HA and NA comes from
there are 13 HA and 9 NA that all circulate in birds, pigs , again and humans
why no B pandemics?
SO FAR NO SHIFT
NO ANIMAL RESERVIOR KNOWN