Viruses are extremely minute sub-living organism, obligate intracellular parasites, seen only
by electron microscope and classified into DNA and RNA viruses.
1-All DNA viruses are double-stranded except for Parvovirus.
2-All RNA viruses are single-stranded except for Birnavirus and Reovirus.
3-RNA viruses have no proof reading capacities so, they are unstable and the mutation rate is
extremely high in them.
4-DNA viruses have well developed proof reading capacities so, they are stable, and the
mutation rate is extremely low in them.
3-Replication of DNA viruses is nuclear while that of RNA viruses is cytoplasmic.
Influenza Viruses and their diseases
Influenza Viruses belong to Orthomyxoviridae "a part of order Myxoviruses" that infect the
body only through the mucous membrane lining the duct systems as digestive, respiratory,
urogenital as well as the eyes.
Orthomyxoviridae are the true Myxoviruses that are characterized by:
-Polymorphic "rounded or ovoid" with 80-120 nanometer diameter.
-Single stranded segmented RNA = sss RNA.
-Enveloped, sensitive to organic solvents, disinfectants and thermolabile hence they loss their
pathogenicity in 3 hrs at 56 degree, in half an hour at 60 degree and in one second at 70 degree.
Influenza viruses are classified according to the number of RNA segments and internal viral
protein "Matrix = M + Non-structural protein = NSP" into three categories A, B, and C.
Pathogenic classification of Influenza Virus type A
Influenza Virus type A are classified according to their pathogenicity into:
1- Highly pathogenic Influenza virus = HPAI: kill 8 from 16; 4-8 wks-old chicks intravenously
injected with virus extract 1/10 through 10 days observation. They include H5 and H7
although some isolates contain H10 "H10N4 & H10N5".
Clincopathologically, they spread rapidly among the susceptible hosts and cause extremely
destructive diseases in the respiratory and digestive systems with high mortalities in short
2-Medium pathogenic Influenza virus = MPAI: kill 1-5 chicks from 16; 4-8 wks-old
intravenously injected with virus extract 1/10 through 10 days observation. Some strains of
them are used for manufacturing vaccines.
3-Low pathogenic Influenza virus = LPAI: they do not cause diseases or may cause very mild
symptoms but if there is concurrent infection between any one of them with Mycoplasma spp.
"Turkey & chickens" or Hemophilus spp." chickens", their pathogenicity will be exaggerated
and may causes disease with mortalities. They do not contain H5 and H7.
Viral receptors of Influenza Virus type A
1-Viruses are obligate intracellular parasites i.e. they can not cause a disease unless enter the
2-Viruses enter the host cells through specific windows “receptors”.
3-Each species of virus has its own specific viral receptors.
4-Influenza virus type A has three viral receptors:
-2, 3 galactosialic acid present on the mucous membranes of respiratory and digestive system
of poultry and swine. It is specific to avian types of Influenza virus.
-2, 6 galactosialic acid present on the mucous membranes of respiratory system of human and
mammals "including swine“. It is specific to human types of Influenza virus.
-1, 6 galactosialic acid present on the mucous membranes of respiratory system of swine. It is
specific to swine types of Influenza virus.
Viral Mixing Vessels
Viral mixing vessels are the animals or birds that may be infected by more than one Influenza
virus type A at the same time. There are three important mixing vessels for Influenza virus A.
They constitute very dangerous threat to human and animal beings due to the probable
genetic changes and production of new Influenza virus type A having the ability to induce an
extremely destructive epidemic and pandemics.
1-Swine: they carry all types of Influenza virus A receptors i.e. 2, 3 galactosialic acid "avian
type" + 2, 6 galactosialic acid "human type" + 1, 6 galactosialic acid "swine type". This means
that they are able to suffer from co-infections either double or triple at the same time.
Double infection as "avian + human types" or "avian + swine types" or "human + swine types".
Triple infection as "avian + human + swine types". During the viruses multiplication inside the
swine host body, genetic exchange and mixing may occur producing a new Influenza virus A
having the ability for human to human transmission. This new Influenza virus type A is a
2-Quail: some literatures mentioned that they contain avian types and human type receptors
and may act as a mixing vessel for these two types producing a new pandemic Influenza virus
type A having the ability for human to human transmission.
3-Human beings: some literatures mentioned that they contain may act as a mixing vessel for
human and swine types producing a new pandemic Influenza virus type A having the ability
for human to human transmission.
NB: turkey and swine have a special unexplained relationship of exchange of influenza virus
“avian types and swine types”. This relationship may act as a mixing vessel for these two
types producing a new pandemic Influenza virus type A having the ability for human to
Molecular Pathogenicity of Influenza viruses
Hemagglutinin facilitates the viral entry to inside the host cell through the connection between
the virus and sialic acid receptor. After connection, the virus is engulfed into the cell through a
process known as endocytosis, after which, the invading virus is attached to the endosomes of
the host cell and start the process of replication and multiplication with induction of the disease.
The virus to be able to invade the host cell, hemagglutinin must be cleaved to H0 & H1.
Process of cleavability is carried out by one of 2 mechanisms:
-The natural mechanisms: in which, hemagglutinin is cleaved by:
1-Proteases: secreted only from lining cells of throat, trachea and lungs.
2-Plasmine: secreted from most cells of the body and sometimes induces the cleavability to
HPIV containing H5 and H7.
-Artificial mechanisms: in which, hemagglutinin is cleaved by trypsine secreted from
Mycoplasma, Hemophilus and/or streptococcus if a concurrent infection occurs including one of
these bacteria and low pathogenic Influenza virus A.
Chacteristics of Influenza Virus type A
I-Genetic reassortment: genetic changes occurring inside the mixing vessels producing a new
pandemic influenza virus type A having the ability for human to human transmission.
II-Virus mutation: Influenza virus type A is highly mutating virus in a relatively short period
of time. Mutation of Influenza virus A has two kinds:
-Antigenic drift = Minor changes: Slow mutation in one or two amino acids of the virus
structure. It occurs either in H or N or never in both.
-Antigenic shift = Major changes: Rapid mutation in the polypeptide chain of virus structure.
It may occur in both H and N epitopes. It takes place in one of 10000 viruses and responsible
for the recurrence of seasonal influenza.
Ecosystem and Reservoirs of Influenza viruses
The ecosystem of influenza viruses means their ability to circulate and transmit among
different species of animal and birds and their ability for species jumping.
This ecosystem includes:
1-Ducks as reservoirs for influenza viruses.
2-Marine mammals as whale and dolphin and land mammals as human, swine and equine as
susceptible mammalian hosts to influenza viruses.
3-Avian species as turkeys, chickens and quails as susceptible hosts.
4-Migratory birds are trans-boundary agents to influenza viruses.
The circulating epitopes and the predominant hosts
Predominant hostsSubtypePredominant hostsSubtype
Diseases of Influenza viruses
1-Avian influenza. 2- Swine Influenza.
3-Equine influenza. 4-Seasonal Influenza.
A-In swine: Acute infectious contagious respiratory disease of swine caused by H1N1, H1N2,
H2N1 or H2N2. It causes high morbidity and low mortality "1-4%". H1N1 is isolated in 1930 in
USA and about 25% of swine population is infected with it. H3N2 is isolated in 1998 and
transmitted from human to swine. Swine are mixing vessels i.e. other avian and human type
can circulate among swine and may produce a new pandemic influenza virus. The disease is
transmitted by direct and direct contact. The mode of infection is by inhalation of infected
droplets. The disease occurs all over the year but its incidence increases in fall and winter
"from October till February".
Acute infectious and contagious respiratory disease caused by H1N1 and characterized by
fever in 80% and chills in 60% of cases, dry cough, chest pain, headache, vomiting, diarrhea
and aches. The disease is more prevalent in fall and winter "from October till February". It
was discovered in 1988 in a pregnant woman died due to pneumonia 8 days after the
admission to the hospital. The study of the case concluded that this woman visited a pig
exhibition 4 days before illness, and 3 nurses contacted with the dead woman were positive to
swine influenza and 75% from exhibitors were also positive. The disease is transmitted by
direct and direct contact with infected swine. The disease is transmitted from human to
human. The mode of infection is by inhalation of infected droplets. The disease affects all ages
but the seriousness is directed toward pregnant women, persons with chronic diseases and
Electron micrograph of avian influenza H5N1 virus
1-The disease is discovered in Italy in 1887 and caused high mortality in birds "fowl plague".
2-The causative agent is denoted as a virus in 1902 but it is truly classified as influenza virus in
1955. The disease was present in Egypt in the fourteens and fifteenth and disappears in the
sixteenth but it reemerges again in 2006.
3-The disease affects chickens, turkeys, quails, ostriches and zoo birds. It also affects swine,
wheals, cats and rats. The migratory birds and aquatic birds are asymptomatic carriers. Pigeon
4-The disease is transmitted by direct and direct contact. The mode of infection is by inhalation
of infected droplets. Mosquitoes and ticks transmit it mechanically. Swine transmit it
biologically especially to turkeys. The incubation periods is 4-14 days.
Natural Reservoirs of Influenza A Viruses
How are these viruses transmitted and maintained in these species?
Transmission: Fecal/Oral route
Heavy fecal shedding by infected ducks - Long term persistence in water - Isolation of AIVs
from surface water
Maintenance: Bird to bird - Persistence in environment.
• Incubation period 3-5 days.
• Severe depression with decreased food and water consumption.
• Drastic decline in egg production.
• Many birds affected.
• Subcutaneous swelling of the head and neck area.
• Nasal and oral cavity discharge.
• Ruffled feathers.
• Swollen, cyanotic (blue) combs and wattles. Conjunctivitis with respiratory sign.
II-Highly pathogenic avian influenza
The disease spread rapidly, morbidity rate reach 100% with mortality may reach 100% within
4-5 days. The mortality is characterized by its exponential fashion.
General signs as enlargement of head with facial edema, cyanosis of unfeathered parts and
drop in egg production. Respiratory signs as coughing, sneezing and nasocular discharge.
Digestive signs as greenish diarrhea. Nervous signs as ataxia.
Clinical Symptoms of Avian influenza
History of influenza in human
1-Spanish flu 1918 – H1N1 – 40 million died – 1 million died in USA.
2-Asian flu 1958 – H2N2 – 1 million died – 70000 died in USA.