Orthomyxoviruses

Retno Budiarti
Microbiology department
FK UHT

Properties

Virion: Spherical, helical nucleocapsid

divided into 3 types: influenza A, B, and C.
The current subtypes of influenza A viruses
found in people are H1N1 and H3N2.
Genome: Single-stranded RNA, segmented
(eight molecules), negative-sense
Proteins: 9 structural proteins, one
nonstructural
Envelope: Contains viral hemagglutinin
(HA) and neuraminidase (NA) proteins

structure

A lipid envelope derived from the cell

surrounds the virus particle.
Glycoprotein :Hemagglutinin (HA) and the
neuraminidase (NA), are inserted into the
envelope and are exposed as spikes about
10 nm long on the surface of the particle.
These glycoproteins are the important Ag
that determine antigenic variation and
host immunity.

structure

Because of the segmented nature of

the genome, when a cell is coinfected
by two different viruses of a given type,
mixtures of parental gene segments
may be assembled into progeny
virions.
This phenomenon, called genetic
reassortment, may result in sudden
changes in viral surface antigens

Hemagglutinin

15 subtypes of HA (H1H15)
binds virus particles to susceptible cells
is the major antigen
ability to agglutinate erythrocytes
The cleavage that separates into HA1 and HA2 is
necessary for the virus particle to be infectious
and is mediated by cellular proteases. Enzymes
that cleave HA are common only at respiratory
tract
The amino terminal of HA2, generated by the
cleavage event, is necessary for the viral
envelope to fuse with the cell membrane, an
essential step in the process of viral infection

Neuraminidase

important in determining the subtype of virus

The spike on the virus particle is a tetramer,
composed of four identical monomers. 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. It facilitates release
of virus particles from infected cell surfaces during
the budding process and helps prevent selfaggregation of virions by removing sialic acid
residues from viral glycoproteins.
Helps the virus through the mucin layer in the
resp tract to reach the target epithelial cells.

Antigenic Drift

Minor antigenic changes

the accumulation of point mutations in the
gene, resulting in amino acid changes in
the protein
Sequence changes can alter antigenic
sites on the molecule such that a virion
can escape recognition by the host's
immune system
A variant must sustain two or more
mutations before a new, epidemiologically
significant strain emerges

Antigenic Shift

major antigenic changes in HA or NA

drastic changes in the sequence of a viral
surface protein
The segmented genomes of influenza
viruses reassort readily in doubly
infected cells
The mechanism for shift is genetic
reassortment between human and avian
influenza viruses

Influenza Virus Replication

Pathogenesis & Pathology

by airborne droplets or by contact with

contaminated hands or surfaces
A few cells of respiratory epithelium are
infected if deposited virus particles avoid
removal by the cough reflex and escape
neutralization by preexisting specific IgA
antibodies or inactivation by nonspecific
inhibitors in the mucous secretions
Within a short time, many cells in the
respiratory tract are infected

Pathogenesis & Pathology

Cell death at later times may also

result from the actions of cytotoxic
T-cells. As a result, the efficiency of
ciliary clearance is reduced,
leading to impaired function of the
mucus elevator; thus there is
reduced clearance of infectious
agents from the respiratory tract.

Pathogenesis & Pathology

The incubation period :1 to 4 days

Viral shedding starts the day preceding onset of
symptoms, peaks within 24 hours, remains
elevated for 12 days, and then declines over the
next 5 days
cellular destruction and desquamation of
superficial mucosa of the respiratory tract but do
not affect the basal layer of epithelium
Viral damage to the respiratory tract epithelium
lowers its resistance to secondary bacterial
invaders, especially staphylococci, streptococci,
and Haemophilus influenzae.

Clinical Findings

Uncomplicated Influenza : Fever (38 40 degrees C), Myalgias, headache,

Ocular symptoms - photophobia, tears,
ache, Dry cough, nasal discharge,
H1N1 strain, the 2009 "swine flu", also
gives rise to gastro-intestinal
symptoms (e.g. vomiting, diarrhea)
Pneumonia

Immunity

long-lived and subtype-specific

Antibodies against HA and NA are
important in immunity to influenza
Immunity can be incomplete, as
reinfection with the same virus can occur
The three types of influenza viruses are
antigenically unrelated and therefore
induce no cross-protection

Laboratory Diagnosis

Isolation and Identification of Virus :

embryonated eggs, Cell cultures can be
tested for the presence of virus by
hemadsorption 35 days after
inoculation
Serology : Antibodies to several viral
proteins (hemagglutinin,
neuraminidase, nucleoprotein, and
matrix)

Avian Influenza

Of the 16 HA subtypes found in birds, only a

few have been transferred to mammals
(H1, H2, H3, and H5 in humans; H1 and H3
in swine; and H3 and H7 in horses).
nine NA subtypes are known for birds, only
two of which are found in humans (N1, N2).
The influenza viruses do not appear to
undergo antigenic change in the birds,
perhaps because of their brief life span.

Avian Influenza..

human pandemic strains have

been reassortants between avian
and human influenza viruses. Pigs
serve as mixing vessels for
reassortants as their cells contain
receptors recognized by both
human and avian viruses

Avian Influenza..

In 1997, in Hong Kong, the first

documented infection of humans by avian
influenza A virus (H5N1) occurred. The
source was domestic poultry.
In 2006, the presence of this highly
pathogenic H5N1 avian influenza virus in
both wild and domestic birds had expanded
to include many countries.
Isolates from human cases have contained
all RNA gene segments from avian viruses,
the avian virus had jumped directly from
bird to human.

treatment

Amantadine hydrochloride,
rimantadine, are M2 ion channel
inhibitors for systemic use in the
treatment and prophylaxis of
influenza A.
The NA inhibitors zanamivir and
oseltamivir for treatment of both
influenza A and influenza B

vaccines

Inactivated viral vaccines are the

primary means of prevention of
influenza
licensed for parenteral use in humans
The vaccine is usually a cocktail
containing one or two type A viruses
and a type B virus of the strains isolated
in the previous winter's outbreaks.

vaccines

Selected viruses strains are grown

in embryonated eggs.
The reassortant virus, which carries
the genes for the surface antigens
of the desired vaccine with the
replication genes from an eggadapted laboratory virus, is then
used for vaccine production

vaccines

Vaccines are either whole virus (WV),

subvirion (SV), or surface antigen
preparations.
The WV vaccine contains intact, inactivated
virus; the SV vaccine contains purified virus
disrupted with detergents; and the surface
antigen vaccines contain purified HA and NA
glycoproteins. All are efficacious.
live attenuated, cold-adapted, temperaturesensitive, trivalent influenza virus vaccine
administered by nasal spray was licensed in
the United States in 2003

Corona virus

enveloped
an unsegmented genome of singlestranded positive-sense RNA
the largest positive strand RNA
viruses
do not grow well in cell culture

Replication:
-

Inside the host cell, the capsid busts

open and releases viral components
single positive strand RNA has a double
role in the viral life cycle of SARS-CoV
because not only it acts as a template
for replication, but also as the first viral
mRNA.
by action of RNA polymerase, the
positive ssRNA is being translated.

The RNA-dependent-RNA polymerase

continues making viral mRNA that
constantly being used to synthesize
viral proteins.
Other viral genes are also being
translated to produce: spike(S),
envelope (E), membrane (M), and
nucleocapsid (N) that binds to the RNA
genome

As a result of this rapid process,

can be used up within hours,
causing the extensive damage and
deterioration of the host cell. At
the same time, SARS-CoV also
replicate their entire genomic RNA
in the cytoplasm of the host cell.

S protein can bind to sialic acid on the

host cell surface which gives the virus a
hemagglutinating ability.
HE protein can cleave the sialic acid from
a sugar chain, which may aid the virus in
escaping from the cell in which it was
replicated
M protein helps in the attachment of the
nucleocapsid to the membranes of
internal structures such as the Golgi Body

Coronavirus Infections in
Humans

tropism for epithelial cells of the

respiratory or gastrointestinal tract
the outbreak of SARS in 2003 was
characterized by serious respiratory
illness, including pneumonia and
progressive respiratory failure
the SARS virus originated in a
nonhuman host and acquired the ability
to infect humans

symptoms

malaise, chills, headache,

dizziness, cough, and sore throat,
followed a few days later by
shortness of breath
The incubation period is 6 days
Death from progressive respiratory
failure