MICROBIOLOGY
Orthomyxovirus
Dr. Quiles
ORTHOMYXOVIRUS NEURAMINIDASE
ssRNA, segmented (8 segments), helical, enveloped Cleaves sialic acid facilitates spread of infection
Negative sense o When sialic acid is cleaved, there will be more HA that will attach
o They cannot undergo transcription unless they produce to the sialic acid, therefore it will facilitate the spread of infection
to the adjacent cells
their own RNA-dependent RNA polymerase because they
cannot access the host cell polymerase Degrades protective layer of mucus in the respiratory tract
3 Groups: Influenza A, B, & C distinguished thru the internal Antibodies produced are non-neutralizing but reduce the spread of
ribonucleoproteins nucleocapsid & matrix proteins infection
o Influenza C is the most antigenically stable group of
orthomyxovirus ANTIGENIC VARIATION
1. Antigenic Drift
o Minor change
SEGMENTS
o Result of changes in the amino acid sequence in the H
Segments 1, 2, 3 – polymerase component
antigen point mutation
Segment 4 – HA Hemagglutinin
Take note that N antigen can also go into antigenic
Segment 5 – NP Nucleocapsid
drift but only in Influenza A
Segment 6 – NA Neuraminidase
Segment 7 – M1 matrix protein o Occur for both Influenza A & B
M2 membrane protein o Outbreaks & Epidemics
M1 – structural protein and promotes assembly of the virus
M2 – facilitates uncoating and HA production
2. Antigenic Shift
– target of amantadine and rimantadine
o Result of the genetic reassortment involving the H antigen
or N antigen (high frequency recombination)
Segment 8 – NS1 & NS2 non-structural proteins
o Occur only in Influenza A
o Responsible for Pandemics & Epidemics
HEMAGGLUTININ (HA)
o Cyclic occurs every 7 to 10 years
Binds with the receptors (Sialic acid and Neuraminic acid)
o Both receptors are acidic which means that if these
Picture on Left:
receptors are alkaline, the HA will not bind to it
Reservoir of Influenza A
Promotes fusion to host cell membrane
Target of neutralizing antibodies Influenza virus have
Agglutinates red blood cells basis for hemagglutination inhibition antigenic variations
test because they have sources
that are different from
human (which are
animals). Any of the virus
within an animal reservoir
that would combine and
undergo genetic
reassortment with humans
will create a “new
serotype”
Picture on Left:
Antigenic Shift
The avian strain will
combine with the human
Picture Above: Illustration of Influenza Virus strain to create a new
Hemagglutinin is colored in purple. Neuraminidase is colored in yellow human strain which
Inside the virus are the 8 segments. Between the capsid and the envelope is creates a new serotype
the matrix protein
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MICROBIOLOGY
Orthomyxovirus
Dr. Quiles
High Pathogenicity Avian Influenza:
1st recognized in Italy in 1878
Extremely contagious in birds
Rapidly fatal
Mortality: Almost 100 % in just a matter of days
H5N1 Influenza in 1997 in China
NOVEL INFLUENZA A H1N1 (2009)
A unique combination of influenza virus genes never previously
identified in either animals or people
Previously referred to the virus as a swine origin influenza virus
Quadruple virus: 2 avian, 1 human, 1 swine virus genes
Resistant to amantadine & rimantadine
Picture Above: Origin of Human Pandemic Influenza A viruses Susceptible to oseltamivir & zanamivir
Verbatim recordings: Initially it started with H2N2, involving the H and the N
antigen. In 1900’s H3 at tsaka N8, hindi na kapareho ng H2N2. So yung sa H
at tsaka N nagkapareho nagkaroon ng change. Tapos nung 1918, H1N1 also
known as “Spanish Flu”, maraming namatay diyan. Nag evolve yan through
the years. Nung 1977, H1N1 or the “”Russian Avian Flu.”
H2N2 nung 1957 na kapareho ng 1889. Take not children, in the future ano
pa ang pwedeng lumabas na mga serotypes? Eto pa rin ang the one in
question
NOTE:
o Among the Influenza viruses, only A and B undergoes antigenic
variations
o Influenza A can undergo both antigenic drift & antigenic shift
o Influenza B only undergoes antigenic drift
INFLUENZA A Picture Above: Genetic Evolution of H7N9 Virus in China, 2013
Subtypes are based on antigenic variation of the surface Verbatim recordings: From the ducks, wild birds & domestic poultry,
glycoproteins nagsama-sama lahat yan, ano ang naging resulta? This is now a new strain
It involves the hemagglutinin and neuraminidase that may infect humans
Current subtypes of Influenza A in humans are H1N1 & H3N2
Influenza A H1N1 & H3N2 & Influenza B strains are included each INFLUENZA
year in the vaccine Commonly called “the flu”
Highly contagious
INFLUENZA VIRUS CLASSIFICATION Illness ranges from mild to severe with life-threatening complications
Influenza A Classification:
Type A Flu Symptoms:
Place of original isolationDate of original isolation Fever and/or chills
Antigen (HA or NA) Headache
E.g. A/Bangkok/ 1/79 (H3N2) Nasal congestion
Sore throat & dry cough
Influenza B Classification: Myalgia or body aches
Type B Malaise or tiredness
Geography GI symptoms – intestinal flu
Date of isolation
E.g. B/Singapore/ 3/64
Question: Why is there no H or N antigen in classification of
Influenza B? Since it only undergoes antigenic drift, it only
involves H antigen, meaning to say, it is automatically understood Picture on Left:
that the antigen involved is the H antigen 1918 Spanish Flu
(Pandemic) H1N1
AVIAN FLU
Caused by 15 subtypes of Influenza A virus subtypes of avian 20-30 million people may
influenza have died worldwide
Can be of low pathogenicity or high pathogenicity
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MICROBIOLOGY
Orthomyxovirus
Dr. Quiles
Treatment:
Amantadine – inhibit uncoating
– target M2 proteins
Picture on Left:
– Influenza A
Mode of
Rimantadine – alternative drug (same MOA as Amantadine)
Transmission of
Oseltamivir – inhibit N antigen H antigen binds to sialic acid
Influenza
clumps no release of virus
– Influenza A & B
– Effective during the 1st 24-48 hours of infection
Zanamivir – same as Oseltamivir
– inhalation
Influenza virus can easily get inside the body through the ICAM1
REFERENCES
receptors which is readily found in our noses
Lecture notes
Complications: Microbiology Manual (2019)
Primary Influenza Pneumonia Dr. Quiles Recordings
Secondary Bacterial Pneumonia
Among the different bacteria that can cause pneumonia, the most common “God pours His love into our hearts to flow out to others’ lives”
bacteria that is associated with influenza are Staphylococcus aureus,
Haemophilus influenzae, & Pneumococcus. But among the 3, the most
common is Staphylococcus aureus
Gullain-Barre syndrome
Reye’s syndrome
Myositis
Myocarditis
Encephalitis
Pericarditis
Most common cause of death in influenza virus infection is Pneumonia
REYE’S SYNDROME
Encephalopathy & liver degeneration
Common complication in children particularly Influenza B, A & VZV
o Among Influenza A and B, it is Influenza B that is commonly
associated with Reye’s syndrome
Associated with intake of aspirin
INFLUENZA VACCINE
Killed vaccine
Contains 2 strains of Influenza A & only 1 strain of Influenza B
o New vaccines today are a combination of 2 strains of Inf.
A & 2 strains of Inf. B
Reformulated each year to contain the current antigenic strain
Protection lasts only for 6 months
o But according to Jawetz: 1 year
PREVENTION & TREATMENT
Prevention: Vaccine
Trivalent or Quadrivalent inactivated or split type vaccine
o Trivalent – 2 A strains; 1 B strain
o Quadrivalent – 2 A strains; 2 B strains
o Take note this is killed or inactivated vaccine
Live attenuated influenza vaccine (LAIV) cold adapted, intranasal
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