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Notes on Orthomyxoviruses
(focused on influenza A virus)
Family Orthomyxoviridae
Genera : Three
Influenza A & Influenza B viruses
Influenza A virus infects many vertebrate species including other mammals & birds.
Is divided into subtypes.
Influenza B virus infects human only and causes similar but milder symptoms.
Influenza A virus share no antigens with Influenza B virus.
Influenza C virus
Influenza C virus infects children, but does not cause significant disease.
Seven segments
HEF: An envelope glycoprotein functions as hemagglutinin, esterase, and fusion protein.
Receptor for influenza C virus is 9-O-Acetyl-N-neuraminic acid (different from that for
influenza A and B viruses)
Tick-borne Orthomyxoviruses
Thogoto virus (6 segments)
Dhori virus (7 segments)
Structure
pleomorphic (spherical/ tubular/ filamentous)
80-120 nm
enveloped
two glycoproteins; hemagglutinin (HA or H), neuraminidase (NA or N)
matrix proteins (M1) line under the envelope
membrane proteins (M2) forming a ion channel
Genome : Segmented
linear, negative sense ssRNA
Influenza A & B viruses : Eight helical nucleocapsid segments. (Each has a looped-end and
is associated with nucleoprotein (NP) and transcriptase (RNA polymerase components: PB1,
PB2, PA) with total size 13.6 kb
segments are in order of size from largest to smallest ones (2340 -890 bases). All code for
one protein except for segments 7 and 8 code two proteins.
499305 (1/2552) S. Saengamnatdej May14, 2009
NA
tetramer
enzyme activity (cleaves SA, prevents clumping, & promotes virus release)
undergoes antigenic changes
subtypes: N1-N9
HA & NA of influenza A virus can undergo major & minor antigenic changes, whereas
influenza B virus undergoes only minor antigenic changes.
[To ensure that one copy of each gene is packed into a virion, segments are enveloped in a
random manner, with 11 segments per virion.]
Pathogenesis
If spreading down further, it can cause severe shedding of bronchial/alveolar epithelium down
to a single-cell basal layer or to the basement membrane.
a transient or low-level viremia is possible, but tissues other than the lung are rarely involved.
The antibody is strain-specific , but cell-mediated immunity is more general (can react same
type). Antibodies to HA is primarily protective, although antibodies to NA is also protective.
Antigenic targets for T-cell responses include peptides from HA but also from the
nucleocapsid protein (NP), PB2 and M1 protein.
Innate immunity
1. mucus
2. continuously beating cilia
3. soluble mannose-binding lectins, lung surfactants, and sialylglycoproteins
4. alveolar macrophages
These are suboptimal in the aged, the premature (very young), the person with an underlying
respiratory problem, smoker, chronically ill, the immunocompromised, and the person with
additional factors including inhaled pollutants, malnutrition, or prior or coincidence infection.
Epidemiology
A/swine/Iowa/3/70(H1N1)
influenza A virus was isolated from a pig in Iowa from isolate number 3 in 1970 with subtypes
H1 and N1.
Pandemic
Pandemic Subtype
1918 HswN1; probable swine flu strain
1947 H1N1
1957 H2N2; Asian flu strain
1968 H3N2; Hong Kong flu strain
1977 H1N1
H5N1 in 1997 avian influenza virus (isolated from 18 humans, caused 6 deaths)
H5N1 not a reassortment, very virulent, passed directly from birds (feces) to man, not man-to-
man transmission.
Reassort with human influenza virus might generate a pandemic.
Most current outbreak is H1N1 subtype in Mexico (see reference 4 for more details)
outbreaks occur every year during winter for only short period (4-6 wks)
Lab Diagnosis
Higher isolaion rate is obtained from throat was, nasal wash, or nasopharyngeal aspirate.
virus isolation in primary monkey kidney cell culture/ Madin-Darby canine kidney cell line
(33-34 ºC, with trypsin),
nonspecific CPE in as quick as 2 days (avg. 4 days)
nonspecific tests: hemadsorption (guinea pig RBC, before CPE), hemagglutination
inhibition of hemadsorption
HI test on the culture supernatant using antisera against the prevalent strains H1N1, H3N2
and type B
serology for seroepidemiology, memory B cells produce antibody against earlier strains can
complicates the interpretation of HI results.
References
1. White DO, Fenner FJ: Chapter 31 Orthomyxoviridae. Medical Virology, 4th ed., San
Diego, 1994, Academic Press. p. 489-499.
2. Sutherland, S. Chapter 49 Orthomyxoviruses. In Greenwood, D, Slack, RCB,
Peutherer, JF (eds.) Medical Microbiology: A guide to microbial infections:
pathogenesis, immunity, laboratory diagnosis and control. 16th ed., Churchill
Livingstone, p.468-474.
3. Murray, PR, Rosenthal, KS, Pfaller, MA. Chapter 60 Orthomyxoviruses. In Murray, PR,
Rosenthal, KS, Pfaller, MA (eds.) Medical Microbiology, 5th ed., Philadelphia, 2005,
Elsevier Mosby. p.609-617.
4. Fraser, C. et al. Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings.
published online. www.sciencexpress.org / 11 May 2009 / Page 5 /
10.1126/science.1176062