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L8 Virus

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L:8 Virology

By
Prof.Dr . Nada Khazal K. Hindi
Introduction to the Viruses
Virology : is the science that deal with the study of viruses, and
focuses on the following aspects of viruses: their structure,
classification and evolution, their ways to infect and exploit host
cells for reproduction, their interaction with host organism
physiology and immunity, the diseases they cause, laboratory
diagnosis, and their use in in production of vaccines and therapy.
Virus are extremely small infective agents, ultramicroscopic.
obligatory intracellular. A complete particle, or virion , has
much simpler structure than a cell. It essentially consist of a block
of genetic material (either DNA or RNA but not both) surrounded
by proteinaceous coat that protects it from the environmental
damage and aid in its transmission from host to host, the protein
coat of virus is called the capsid. The capsid composed from
subunits called capsomers, designed to protect the genome, the
capsid and nucleic acid called Nucleocapsid. Virus have the capacity
for infecting and replicating in animal, plant and bacterial cells. The term
virus was coined by Pasteur, and is from the Latin word for poison.
The pathogenicity of a virus depends on a great variety of structural
and functional characteristics. Therefore, even within a closely
related group of viruses, different species may produce
significantly distinct clinical pathologies.
Some viruses are enveloped & other unenveloped ( Naked
viruses).An important structural feature used in defining a viral
family is the presence or absence of a lipid-containing membrane
surrounding the nucleocapsid. This membrane is referred to as
the envelope. A virus that is not enveloped is referred to as a
naked virus. In enveloped viruses, the nucleocapsid is flexible
and coiled within the envelope, resulting in most such viruses
appearing to be roughly spherical. The envelope is derived
from host cell membranes. However, the cellular membrane
proteins are replaced by virus-specific proteins, conferring virus-
specific antigenicity upon the particle
 Envelope is lipoprotein in nature (Lipid and proteins),
 *The envelope is derived from host cell membrane when virus is
released by budding.
Peplomers (Envelope spikes): These are glycoprotein
projections, bind to cell surface proteins
*There are two major structures of viruses
*Enveloped virus
*Naked non enveloped virus
**Enveloped viruses are more sensitive to heat, drying,
detergent and lipid solvents such as alcohol and ether than
non-enveloped virus
 Note:
 Viruses containing lipid envelopes are sensitive to damage
by harsh environments and, therefore, tend to be transmitted
by the respiratory, parenteral, and sexual routes. Nonenveloped
viruses are more stable to hospital environmental conditions and
often transmitted by the fecal-oral route.
 Virion: is a complete virus particle combining these structural
elements.
 Prions: This infectious protein is designated the prion protein
without nucleic acid.
 Viriod: This infectious nucleic acid without protein.
•Viruses have a host range: adapted to specific organisms that is,
viruses infect specific cells or tissues of specific hosts, specific
animal or specific plants.
***Viral specificity: refers to the specific kinds of cells a virus can
infect. It is regulated by the specificities of attachment, penetration
and replication of the virus (Receptors Properties of viruses)
 Genome
The type of nucleic acid found in the virus particle is perhaps the most
fundamental and straightforward of viral properties. It may be RNA or DNA,
either of which may be single-stranded (ss) or double-stranded (ds). The most
common forms of viral genomes found in nature are ssRNA and dsDNA.
However, both dsRNA and ssDNA genomes are found in viruses of medical
significance. Single-stranded viral RNA genomes are further subdivided into those
of positive polarity (+RNA: that is, of messenger RNA sense, which can
therefore be used as a template for protein synthesis), and those of negative
polarity or are antisense (- RNA: that is, complementary to messenger RNA
sense, which cannot therefore be used directly as a template for protein
synthesis). Viruses containing these two types of RNA genomes are commonly
referred to as positive-strand and negative-strand RNA viruses, respectively.
Genome of N A of virus
1. DS RNA
2. SS RNA
3. DS DNA
4. SS DNA
The general properties of viruses:
1. *The virus contains one type of nucleic acid, either RNA or
DNA but never both
2. *All viruses have a protein coat (capsid) that surrounds and
protects the nucleic acid core.
3. *Some viruses have a lipid envelope or membrane
surrounding a nucleocapsid core. *The source of the envelope is
from the membranes of the host cell.
4. Viruses are not cells; do not possess cellular organelles as,
mitochondria, ribosomes or other cellular components
5. ***They do not encode their own protein synthesis
machinery (ribosomes) and energy-generating metabolic pathways.
**They depend upon protein synthetic machinery of host cells
6. *Viruses replicate or multiply only within living cells (Viruses
are obligate intracellular)
7. ***They are unaffected by antibiotics.
8. They are sensitive to interferon
The general properties of viruses:
9.*Viruses do not reproduce by binary fission, but they replicate by
complex process in the living cells that they infect
10.***Viruses do not grow (have constant size and shape)
11.* Ultra-filterable, very small size, i.e. they are not retained by bacteria-
proof filters.
12.*Viruses are very small units with diameters of about 16 nm to over 300
nm as poxviruses
13.*Ultramicroscopic, can only be seen with electron microscope
14. They possess the genes to invade and regulate the metabolic
activity of host cells. e.g// • Ex. Hepatitis B (4 genes) and herpesviruses
(100 genes)
15.*They have genetic information encoding their structural components,
16. Some of the viruses also possess genes that code for several
regulatory active proteins (such as trans-activators) and enzymes (e.g.
proteases and polymerases. e.g. RNA dependent- RNA polymerase
Figure show viruses
 Structure and symmetry of virus:
 Type of symmetry of the virus capsid, capsids normally
have one of three shapes
 1.icosahedral ( as in the poliovirus ).
 2-helical ( as in the tobacco mosaic virus)
 3.complex(as in the bacteriophages , or phages ).

Figure show viral shapes


Figure show viral nucleocapsid symmetry
 Method of replication
These groups are designated by Roman numerals and discriminate viruses
depending on their mode of replication and genome type
General Steps in Viral Multiplication (Viral production,
Replication):- Viruses multiply only in living cells. The host cell must provide
the energy and protein synthetic machinery and the low molecular-weight
precursors for the synthesis of viral proteins and nucleic acids.
**The virus replication occurs in six main stages:
1. Attachment or Adsorption : is a specific binding between viral capsid
protein and specific receptors on the host cellular receptors.
2.Penetration: viruses enter the host cell through receptor-mediated
endocytosis or membrane fusion
3.Uncoating: the viral capsid is degraded by viral enzyme or host enzymes
thus releasing the viral genomic nucleic acid
4.Replecation: synthesis of viral messenger RNA (mRNA) for viruses
except positive sense RNA viruses
5.Assemble: viral protein synthesis, assemble of viral protein and genome
6.Release: viruses are released from the host cell by lyses. Enveloped
viruses (e,g, HIV) typically are released from the host cell by budding .
Once the virus infects a given cell, there are two cycles
that the virus can follow:
1)The lytic cycle: (cytocidal infection) involves using the
organelles and machinery of the cell to assemble new viruses,
which eventually ruptures the cell and releases the virions
into the outside environment.
2)The lysogenic cycle: Some viruses undergo a lysogenic
cycle (dormant or latent) where the viral genome is
incorporated by genetic recombination into a specific place in
the host's chromosome. The viral genome is then known as a
"provirus", The viral genome is mostly silent within the host.
But when reactivated in response to environmental stimuli
(e.g., heat, ultraviolet irradiation, or chemotherapy) cause cell
lysis and release of viral progeny. E.g. AIDS (HIV infection).
E.g. Bacteriaphages
****Effects of viruses on host cell:
Cytopathic effects (CPE): (Morphologic Effects) : is the changes in cell
morphology caused by infecting virus for e.g. rounding of the infected
cell, fusion with adjacent cells to form a syncytia (polykaryocytes), and the
appearance of nuclear or cytoplasmic inclusion bodies.
Effects on Cell Physiology: The interaction of virus with the cell
membrane may change the physiological parameters of infected cells,
including movement of ions, formation of secondary messengers, and
activation cascades leading to altered cellular activities.
Effects on cell biochemistry: Many viruses inhibit the synthesis of host
cell macromolecules, including DNA, RNA, and protein and cellular
transcriptional activity.. etc.
Genotoxic Effects: Following virus infection, breakage, fragmentation,
rearrangement and/or changes in the number of chromosomes may occur.
Biologic Effects: Virus-specified proteins may alter the cell's antigenic or
immune properties, shape, and growth characteristics.
Persistent Infections:
In a persistent infection the virus is not eliminated from all of the host
tissues after initial infection or the acute phase of disease.
****There are several types of persistent infection:
1)Latent Infection: Some viruses undergo a lysogenic cycle ( dormant)
where the viral genome is incorporated by genetic recombination into a
specific place in the host's chromosome. The viral genome is then known
as a "provirus", The viral genome is mostly silent within the host. But
when reactivated in response to environmental stimuli (e.g., heat,
ultraviolet irradiation, or chemotherapy) cause cell lysis and release of
viral progeny. E.g. AIDS (HIV infection)
3)Chronic Infection: The cellular effects of chronic infection are usually
the same as those of acute cytocidal infections, except that production of
progeny may be slower, and limited to a few cells. The long-term cellular
changes may result in severe disease, immune suppression. e.g. HCV
infection
3)Slow Infection: This type of virus-cell interaction is characterized by a
prolonged incubation period, and slow progression of cellular injury and
disease. e.g. measles
4)Transforming Infections:DNA or RNA tumor viruses may mediate
multiple changes that convert a normal cell into a malignant phenotype.
Viral-like particles (VLPs):
•***VLPs are nanoscale structures made up of assembled viral proteins
that lack viral genetic material and are therefore non-infectious.
• VLPs are dispersed nanomaterials that can be produced in a
variety of systems, including mammals, plants, insects, and bacteria.
•***VLPs can be exploited as carriers for the delivery of bio- and
nanomaterials, such as drugs, and vaccines
VLP types:
**Application of VLPs is their potential in vaccinology where they can
offer several advantages over conventional vaccine approaches, because of
1. *Their size and shape, which resembles the actual size and shape of
native viruses,
2. *VLPs can efficiently elicit the immune responses
3. *VLPs lacking viral genomes, there is no potential for replication
within the target cells, which improved safety especially for immune-
compromised or elderly vaccines
4. *VLPs can stimulate both humoral and cellular immune response.
Sub-viral particles (viroid and prion):
1. Viroids:
**Plant viruses resemble animal viruses in many aspects:
*Plant viruses are morphologically similar to animal viruses, and they have
similar types of nucleic acid
***Some plant diseases are caused by viriod
**viroids; are short pieces of naked RNA,The RNA does not code for any
proteins. Thus viroids have been pathogens only for plants
2. Prions:
A few infectious diseases are caused by prions.
*In 1982, American neurobiologist Stanley Prusiner proposed that
proteinaceous infectious particle caused a neurological disease in sheep called
scrapie
*The infectivity of scrapie-infected brain tissue is reduced by treatment with
proteases but not by treatment with radiation, suggesting that the infectious
agent is pure protein.
*Prion not affected by Radiation, and chemical agents
Sub-viral particles (viroid and prion):
*Caused nine animal diseases, All nine are neurological diseases called
spongiform encephalopathies because large vacuoles develop in the brain ,
including the“mad cow disease”that emerged in cattle in Great Britain in 1987.
The human diseases are :
*kuru, Creutzfeldt-Jakob disease (CJD),
* Gerstmann-SträusslerScheinker syndrome,
*Fatal familial insomnia.
***These diseases run in families, which indicates a possible genetic cause.
*They cannot be purely inherited, because mad cow disease arose from feeding
scrapie-infected sheep meat to cattle, and the new (bovine) variant was
transmitted to humans who ate undercooked beef from infected cattle.
* CJD has been transmitted with transplanted nerve tissue and
contaminated surgical instruments.
*These diseases are caused by the conversion of a normal host glycoprotein
called PrPC into an infectious form called PrPSc
Figure show prions and viroids
Viruses can be classified according to
1. *the host cell they infect:
a.* animal viruses
b. *plant viruses
c. *fungal viruses
d. *bacteriophages: (viruses infecting bacteria which include the most
complex viruses).
*Another classification is based mainly on characteristics of structure of
the viral particles, including:
a. *capsid shape, or symmetry (icosahedral , helical or complex).
b. *envelope: Presence or absence of lipid envelope. (enveloped, or
naked)
c. *the type of nucleic acid (DNA or RNA, double stranded (ds) or
single stranded (ss),
d. the process of replication.
Baltimore classification : Baltimore classification (first defined in 1971):
Named after David Baltimore, a Nobel Prize-winning biologist.
**Transmission of Viruses:
1. Respiratory transmission (Droplet contact) e.g. Influenza A,
common cold
2. Faecal-oral transmission: Enterovirus (HAV)
3. Iatrogenic transmission due to medical procedures, e.g:
transplantation of infected material and blood transfusion e.g.
HBV, or HCV
4. Sexual Transmission: HIV
5. Animal or insect vectors: Rabiesvirus
The types Vaccines
1) live, attenuated microorganisms;
2) killed microorganisms
3) microbial extracts
4) vaccine conjugates
5) inactivated toxins (toxoids)
6)DNA vaccine
Family Viruses Type of NA Diseases
Pox viruses Variola DNA smallpox

Herpes simplex
DSDNA Cold, genital sores, encephalitis
type1&2

Varicella-zoster DSDNA Chickenpox, shingles


herpes viruses
Cytomegalic inclusion disease of neonates,
Cytomegalovirus DSDNA
pneumonia in immunocompromised patients

Epstein- Barr (EB) DSDNA Infectious mononucleosis (cancer)


Adeno viruses Adeno viruses DNA Sore throat, conjunctivitis, hemorrhagic cystitis
Papova viruses Papilloma DNA Warts, cervical cancer

Hepadna viruses Hepatitis B DSDNA Hepatitis B, liver cancer


Hepatitis C SSRNA
Hepadna viruses Hepatitis
Hepatitis D SSRNA
Hepadna viruses Hepatitis

Picorna viruses Hepatitis A SSRNA


Hepatitis

SSRNA
calicivirdae Hepatitis E Hepatitis

Reo viruses Rota viruses DSRNA Causes diarrhea in infant


Family Viruses Type of NA Diseases

Picorna viruses rhino viruses RNA Common cold

Human immuno-
Retero viruses (HIV) SSRNA AIDS
deficiency viruses

Rhabdo viruses rabies viruses RNA Causes human rabies

sterility., encephalitis, swelling of the parotid


Mumps RNA
paramyxo viruses glands

Measles RNA (rash, maculopapules)

Influenza A,B RNA


orthomyxovirus influenza
ParaInfluenza SSRNA
Togo viruses Rubella SSRNA Causes measles in children (rash)
RNA
Ebola virus Ebola virus Hemorrhagic fever

DNA
Zika virus Zika virus Guillain-Barre syndrome

SSRNA
Corona virus Corona virus Respiratory failure, Common cold

Picornaviridae SSRNA

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