Download (1) Replication of negative ssRNA viruses

Lec 7
virology
Negative single strand RNA viruses
*General and Molecular characteristics
1-Medically important negative-strand RNA viruses
2- They are all enveloped; .
3-Their virions contain an RNA-dependent RNA polymerase
(transcriptase) that synthesizes viral mRNAs using the genomic
the genomic negative-strand viral negative-strand RNA as a template
RNAs are not infectious,
4- Some negative-strand RNA viruses have segmented genomes, whereas
others have nonsegmented genomes .
5- Negative ssRNA viruses include many important medically families
such as Paramyxoviridiae ( e.g : parainfleunza 1-5 ,mumps, measles ) ,
Orthmyxoviridae (e.g : influenza H1N1),
Rhabdoviridae (e.g Rabies virus ) and Filoviridae ( e.g : Ebola virus )
6-The v irion contains five proteins, one of which, the G (for “glyco-“)
protein, is an envelope protein composed of viral spikes . The rabies
virion attaches via its glycoprotein spikes to cell-surface receptors.
Note : Although most of these viruses replicate in the cytosol, the
replication of influenza virus RNA (an orthomyxovirus occurs in the
nucleus )
*Replication of negative- ssRNA virus genome:
1- the first step in the replication of negative-strand RNA viruses is the
synthesis of mRNAs by RNA dependent RNA polymerase presence in
virus particle whereas with positive-strand RNA viruses, the first step in
replication is translation of the incoming genomic RNA.
2- Translation the new mRNA (+RNA) into viral protein including
capsid protein .
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3- New mRNA serve as templete for synthesis (- RNA ) by same
enzyme.
4- Assembly into necleocapsid
5- releasing from infected host cell .
Figure (1) Replication of negative ssRNA viruses .
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*Some families of Negative ssRNA viruses
1-Rhabdovirdae :
are enveloped, bullet-shaped viruses each contains a helical
nucleuocapsid . The viruses in the family Rhabdoviridae known to infect
mammals are divided into two genera: Lyssa virus (rabies virus, the
rhabdovi us of greatest medical importanceto humans), and Vesiculovirus
[vesicular stomatitis virus (VSV), a virus of horses and cattle, Other rha
bdovir uses infect invertebrates, plants, or other
vertebrates.
*Rabies virus
*Epidemiology
A wide variety of wildlife, such as, squirrels, foxes,and bats, provide
reservoirs for the rabies virus. In developing countries, domestic dogs
and cats also constitute important reservoirs for rabies. Humans are
usually infected by the bite of an animal, but, in some cases, infection is
via inhalation (for example, of droppings from infected bats).
*Pathogenesis:
1-Following inoculation, the virus may replicate locally but then travels
via retrograde transport within peripheral neurons to the b rain,
2- it replicates primarily in the gray matter .
3-From the brain, the rabies virus can travel along autonomic nerves,
leading to infection of the lungs, kidney, adrenal medulla, and salivary
Glands.
4-The extremely variable incubation period depends on the host’s
resistance, amount of virus transferred, and distance of the site of initial
infection from the central nervous system (CNS). Inc ubation generally
lasts 1 to 8 weeks but may range up to several months.
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*Clinical illness
1-May begin with an abnormal sensation at the site of the bite.
2-Then progress to a fatal encephalitis, with neuronal degeneration of the
brain and spinal cord.
3-Symptoms include hallucinations; seizures; weakness; mental
dysf unction.
4-paralysis. coma; and, finally, death. Many, but not all, patients show the
classic rabid sign of hydrophobia.
Figure (2) : Schematic representation the pathogenesis of rabies
infection.
*Laboratory identification
1-clinical diagnosis may be difficult. Postmortem, in approximately 80
percent of cases, characteristic eosinophilic cytoplasmic inclusions
Negri bodies) may be identified in certain regions of the brain
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2-These cytoplasmic inclusion bodies are virus production foci and
diagnostic of rabies .
3-The diagnosis can be made by identification of viral antigens in
biopsies of skin from the back of the neck or from corneal cells or by
demonstration of the viral nucleic acid by reverse transcription
polymerase chain reaction (RT-PCR) in infected saliva.
Figure (3): An oval Negri body in a brain cell from a human rabies case
2-Paramyxoviridae :
Paramyxov iruses are spherical, enveloped particles that contain a
nonsegmented, negative-strand R N A genome
(Paramyxo viridae typically consist of a helical nucleocapsid surrounded
by an envelope that contains two types of integral membrane or envelope
proteins. The first, the H N protein (H stands for
hemagglutinin and N for neuraminidase), is involved in the binding of
the virus to a cell. [Note: Measles virus lacks the neuraminidase
activity.] The second, the F protein (F stands for f usion)
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*Mumps virus: Mumps used to be one of the commonly acquired
childhood infections. Adults who escape the disease in childhood
could also be infected. In the prevaccine period, mumps was the
most common cause of viral encephalitis. Complete recovery,
however, was almost always achieved. The virus spreads by
respiratory droplets. Although about one third of infections are
subclinical,
the classic clinical presentation and diagnosis center on
infection and swelling of the salivary glands, primarily the parotid
glands. However, infection is widespread in the body and may involve
not only the salivary glands but also the pancreas, CNS, and testes.
Orchitis (inflammation of the testis) caused by mumps virus may cause
sterility. A live, attenuated vaccine has been available for many year and
has resulted in a dramatic drop in the number of cases of mumps. [Note:
Individuals who have had the disease develop lifelong immunity
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3-Orthomyxoviridae :
Orthomyxoviruses are spherical, enveloped viruses containing a
segmented, negative strand RN A genome. Viruses in this family infect
humans, horses, and pigs, as well as nondomestic waterfowl, and are
the ca use of influenza. Orthomyxo vir uses are di vided into three
types: influenza A, B, and C. Only influenza virus types A and B are
of medical importance. Type A influenza viruses differ from type B
viruses in that they ha v e an animal reservoir and are divided into
subtypes. Influenza vi us C is not a significant human pathogen.
Structure
Influenza virions are spherical, en veloped, pleomorphic particles
Two types of spikes project from the s urface: One is composed of H
protein and the second of N protein. [Note: This is in contrast to the
paramyxoviruses, in which H and N activities reside in the same
spike protein.] Both the H and N influenza proteins are integral
membrane proteins. The M (matrix) proteins underlie the
viral lipid membrane. The RNA genome, located in a helical nucleocapsid, is composed of eight distinct segments of R N A, each of
which encodes one or more viral proteins. Each nucleocapsid segment
contains not only the viral R NA but also four proteins ( NP, t h e
major nucleocapsid protein, and three P (polymerase) proteins that
are present in much smaller amounts than NP and are involved in
synthesis and replication of viral R NA).
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Figure (4): Influenza virus by Electron micro-graph. and Schematic
drawing showing envelope proteins called H and N spikes that protrude
from the surface. M protein = matrix protein.
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