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. Most of the
segments code for a single protein
 Proteins: 9 structural proteins, one
nonstructural
 Envelope: Contains viral hemagglutinin (HA)
and neuraminidase (NA) proteins
 Antigenic changes continually occur
within the type A and lesser degree in
the type B, type C antigenically stable.
 Influenza A strains are also known for
aquatic birds, chickens, ducks, pigs,
horses, and seals. Some strains isolated
from animals are antigenically similar to
strains in the human population.
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.
 The glycoproteins are the important Ag that
determine antigenic variation and host immunity,
mediates virus attachment to cells; activated by
cleavage;
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 (H1–H15)
 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 self-aggregation 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 1–2 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 3–5 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
 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, temperature-
sensitive, trivalent influenza virus vaccine
administered by nasal spray was licensed in
the United States in 2003
Corona virus
 enveloped
 an unsegmented genome of single-
stranded 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
Thank you....