Orthomyxoviridae
The Orthomyxoviridae (influenza viruses) are a major
determinant of morbidity and mortality caused by respiratory
disease, and outbreaks of infection sometimes occur in worldwide
epidemics. Influenza has been responsible for millions of deaths
worldwide. Mutability and high frequency of genetic reassortment
and resultant antigenic changes in the viral surface glycoproteins
make influenza viruses formidable challenges for control efforts.
The Orthomyxoviridae (orthos, Greek for "straight"; myxa,
Greek for "mucus")are a family of RNA viruses that includes five
genera: Influenzavirus A, Influenzavirus B, Influenzavirus C,
Isavirus and Thogotovirus. .The first three genera contain viruses
that cause influenza in vertebrates, including birds, humans, and
other mammals. Isaviruses infect salmon; thogotoviruses infect
vertebrates and invertebrates, such as mosquitoes and sea lice.
Properties of Orthomyxoviruses
Important properties of Influenza viruses are summarized as
following :
Virion: Spherical, pleomorphic, 80–120 nm in diameter (helical
nucleocapsid, 9 nm)
Composition: RNA (1%), protein (73%), lipid (20%), carbohydrate
(6%)
Genome: Single-stranded RNA, segmented (eight molecules),
negative-sense, 13.6 kb overall size
Proteins: Nine structural proteins, one nonstructural
Envelope: Contains viral hemagglutinin (HA) and neuraminidase
(NA) proteins
Replication: Nuclear transcription; capped 5' terminal of cellular
RNA scavenged as primers; particles mature by budding from
plasma membrane
Outstanding characteristics:
Genetic reassortment common among members of the same genus
Influenza viruses cause worldwide epidemics
Classification
In a phylogenetic-based taxonomy the "RNA viruses" includes
the "negative-sense ssRNA viruses" which includes the Order
"Mononegavirales", and the Family "Orthomyxoviridae" . The
genera-associated species and serotypes of Orthomyxoviridae are
shown in the following table.
Orthomyxoviridae Genera, Species, and Serotypes
Species (* indicates Serotypes
or
Genus
Hosts
type species)
Subtypes
H1N1,
H1N2,
H2N2,
H3N1,
H3N2,
H3N8,
H5N1,
H5N2,
Influenzavirus
Human, pig,
Influenza A virus* H5N3,
H5N8,
A
bird, horse
H5N9,
H7N1,
H7N2,
H7N3,
H7N4,
H7N7,
H9N2, H10N7
Influenzavirus
Influenza B virus*
Human, seal
B
Influenzavirus
Influenza C virus*
Human, pig
C
Infectious salmon
Atlantic
Isavirus
anemia virus*
salmon
Thogoto virus*
Tick,
mosquito,
Thogotovirus
Batken virus, Dhori mammal
Dhori virus
(including
virus
human)
Quaranfil
virus,
Johnston
Atoll
virus, Lake Chad
virus
Influenza A
Influenza A viruses are further classified, based on the viral
surface proteins hemagglutinin (HA or H) and neuraminidase (NA or
N)... Sixteen H subtypes (or serotypes) and nine N subtypes of
influenza A virus have been identified.
Diagram of influenza nomenclature.
Further variation exists; thus, specific influenza strain isolates are
identified by a standard nomenclature specifying virus type,
geographical location where first isolated, sequential number of
isolation, year of isolation, and HA and NA subtype.
Examples of the nomenclature are:
1. A/Brazliane/59/2007 (H1N1)
2. A/Moscow/10/99 (H3N2)
The type A viruses are the most virulent human pathogens among
the three influenza types and causes the most severe disease. The
serotypes that have been confirmed in humans, ordered by the
number of known human pandemic deaths, are:







H1N1 caused "Spanish Flu" in 1918, "Swine flu" in 2009.
H2N2 caused "Asian Flu".
H3N2 caused "Hong Kong Flu".
H5N1 is a pandemic threat.
H7N7 has unusual zoonotic potential
H1N2 is endemic in humans and pigs.
H9N2, H7N2, H7N3, H10N7.
Influenza B
Influenza B virus is almost exclusively a human pathogen, and is
less common than influenza A. The only other animal known to be
susceptible to influenza B infection is the seal. This type of influenza
mutates at a rate 2-3 times lower than type A and consequently is less
genetically diverse, with only one influenza B serotype As a result of
this lack of antigenic diversity, a degree of immunity to influenza B is
usually acquired at an early age.
Influenza C
The influenza C virus infects humans and pigs, and can cause
severe illness and local epidemics. However, influenza C is less
common than the other types and usually seems to cause mild disease
in children.
Structure & Function of Hemagglutinin
The HA protein of influenza virus binds virus particles to
susceptible cells and is the major antigen against which neutralizing
(protective) antibodies are directed. Variability in HA is primarily
responsible for the continual evolution of new strains and subsequent
influenza epidemics. Hemagglutinin derives its name from its ability
to agglutinate erythrocytes under certain conditions.
The amino acid sequence for HA can be calculated from the
sequence of the HA gene, and the three-dimensional structure of the
protein has been revealed by x-ray crystallography, so it is possible to
correlate functions of the HA molecule with its structure.
The primary sequence of HA contains 566 amino acids A short
signal sequence at the amino terminal inserts the polypeptide into the
endoplasmic reticulum; the signal is then removed. The HA protein is
cleaved into two subunits, HA1 and HA2, that remain tightly
associated by a disulfide bridge. A hydrophobic stretch near the
carboxyl terminal of HA2 anchors the HA molecule in the
membrane, with a short hydrophilic tail extending into the
cytoplasm. Oligosaccharide residues are added at several sites.
Structure & Function of Neuraminidase
The antigenicity of NA, the other glycoprotein on the surface of
influenza virus particles, is also important in determining the
subtype of influenza virus isolates.
The spike on the virus particle is a tetramer, composed of four
identical monomers . A slender stalk is topped with a box-shaped
head. There is a catalytic site for NA on the top of each head, so that
each NA spike contains four active sites.
The NA functions at the end of the viral replication cycle. It is a
sialidase enzyme that removes sialic acid from glycoconjugates. It
facilitates release of virus particles from infected cell surfaces during
the budding process and helps prevent self-aggregation of virions by
removing sialic acid residues from viral glycoproteins. It is possible
that NA helps the virus negotiate through the mucin layer in the
respiratory tract to reach the target epithelial cells