VIRUS

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In 1898, Friedrich Loeffler and Paul Frosch found evidence that the
cause of foot-and-mouth disease in livestock was an infectious particle
smaller than any bacteria. This was the first clue to the nature of
viruses, genetic entities that lie somewhere in the grey area between
living and non-living states.

Viruses depend on the host cells that they infect to reproduce. When
found outside of host cells, viruses exist as a protein coat or capsid,
sometimes enclosed within a membrane. The capsid encloses either
DNA or RNA which codes for the virus elements. While in this form
outside the cell, the virus is metabollically inert; examples of such
forms are pictured below.
When it comes into contact with a host cell, a virus can insert its genetic material
into its host, literally taking over the host's functions. An infected cell produces
more viral protein and genetic material instead of its usual products. Some viruses
may remain dormant inside host cells for long periods, causing no obvious change in
their host cells (a stage known as the lysogenic phase). But when a dormant virus is
stimulated, it enters the lytic phase: new viruses are formed, self-assemble, and
burst out of the host cell, killing the cell and going on to infect other cells. The
diagram below at right shows a virus that attacks bacteria, known as the lambda
bacteriophage, which measures roughly 200 nanometers.
Icosahedral symmetry Complex symmetry

Helical symmetry
Anatomy of a Virus
• The tiniest viruses are
20 nm in diameter.
(smaller than a
ribosome)

• They consist of
nucleic acids enclosed
in a protein coat and
sometimes a
membranous envelop.
• The genomes (sets of genes) maybe
– Double stranded DNA
– Single stranded DNA
– Double stranded RNA
– Single stranded RNA
• They are called either a DNA or RNA virus
depending on the type of nucleotide in the
make-up.
• They may be linear or circular
• The smallest have only 4 genes and largest
have several hundred.
• Capsid – a protein shell that covers the viral
genome. They may be
– Rod-shaped
– Polyhedral
– More complex

Capsids are built from large numbers of protein

subunits called CAPSOMERES
The most complex capsids are found in viruses
that infect bacteria – BACTERIOPHAGES
(T1-T7). They have a protein tail piece with
tail fibers that attach to the bacterium
 Virion Structure

• Nucleic acid
– DNA or RNA
• Capsid
– Capsomeres
• Envelope
• Spikes

Figure 13.2a
Morphology of a Polyhedral
Virus

Figure 13.2
Polyhedral Viruses

Figure 13.16a
Morphology of an Enveloped
Virus

Figure 13.3
Enveloped Viruses

Figure 13.16b
Morphology of a Helical Virus

Figure 13.4
Morphology of a Complex Virus

Figure 13.5
 Reproduction
• Viruses are obligate
intracellular parasites
that can reproduce only
within a host cell.
• They do not have
– Enzymes for metabolism
– Do not have ribosomes
– Do not have the
equipment to make
proteins
 Each type of virus can infect and parasitize
only a limited range of host cells called its
HOST RANGE.
• Some are broad based while others are not.
– Swine flu virus can infect swine or humans
– Rabies can infect may mammals
• Some can parasitize only E. coli
• Eukaryote viruses are usually tissue specific
• Viruses use a “lock and key” fit to identify
hosts.
 Reproduction occurs using lytic
or lysogenic cycles
• The Lytic Cycle • The Lysogenic Cycle
– Culminates in the death – Replication of the viral
of the host cell genome without
– Virulent viruses destroying the host
reproduce only by lytic cell.
cyle.
– A temperate virus may
– Natural selection favors
bacterial mutations with reproduce by either
receptor sites that are cycle.
resistant to a particular – Lambda virus:
phage or that have resembles T4 but only
restriction enzymes to has a single short tail
destroy the phages. fiber
 Lytic Cycle of a T-Even
Bacteriophage
1

Figure 13.11
 Lytic Cycle of a T-Even
Bacteriophage

Figure 13.11
• While phages have the potential to wipe out
a bacterial colony in just hours, bacteria
have defenses against phages.
– Natural selection favors bacterial mutants with
receptors sites that are no longer recognized by
a particular type of phage.
– Bacteria produce restriction nucleases that
recognize and cut up foreign DNA, including
certain phage DNA.
• Modifications to the bacteria’s own DNA prevent its
destruction by restriction nucleases.
– But, natural selection favors resistant phage
mutants
• In the lysogenic cycle, the phage genome
replicates without destroying the host cell.
• Temperate phages, like phage lambda, use
both lytic and lysogenic cycles.
• Within the host, the virus’ circular DNA
engages in either the lytic or lysogenic
cycle.
• During a lytic cycle, the viral genes
immediately turn the host cell into a virus-
producing factory, and the cell soon lyses
and releases its viral products.
 Results of Multiplication of
Bacteriophages
• Lytic cycle
– Phage causes lysis and death of host cell
• Lysogenic cycle
– Prophage DNA incorporated in host DNA
– Phage conversion
– Specialized transduction
The Lysogenic Cycle

Figure 13.12
Generalized Transduction

Figure 8.28
Specialized Transduction

Figure 13.13
 Lambda reproduction
• Infects an E. coli cell by injecting its DNA
• The lambda DNA molecule forms a circle.
• Lytic or lysogenic cycles begin
• In a lytic cycle, the cell is turned into a lambda
producing factory, the cell lyses and releases its
products.
• In a lysogenic cycle, the viral genome is
incorporated into by genetic recombination into a
specific site on the host cell’s chromosome.
• It is now known as a prophage
• Every time the E. coli divides, it replicated the
phage DNA and passes it along to the daughter
cells.
• This enables the phage to replicate without
destroying the host.
• The phages may at some point in time become
active phages that lyse their host cell and releasing
infectious particles.
• There is usually an environment trigger.
• There may be other prophages released as well and
this may change the phenotype of the host. This is
of medical importance. Examples: diphtheria,
botulism and scarlet fever.
• Regardless of the type of virus, the parasite
diverts the host cell’s resources for viral
production.
• The host cell provides:
• Nucleotides for nucleic acid production
• Enzymes
• Ribosomes
• tRNA
• Amino acids
• ATP
 Modes of infection and replication of
animal viruses
• Focus on animals viruses with
a viral envelop
– The envelop is outside the capsid
and helps the virus enter the host
cell.
– Generally a lipid bilayer with
glycoprotein spikes
– The envelop fuses with the cell
membrane
– The ER of the host cell makes the
membrane proteins which are
transported to the membrane
– New viruses exits the host in a This reproductive cycle
process similar to exocytosis. does not kill the host.
• Some viruses have envelopes that are not
derived from the plasma membrane.
• Herpesvirus has an envelop that is derived
from the nuclear membrane.
• These become integrated into the host
genome as a provirus. Once these viruses
are acquired they tend to reoccur through
out a person’s life.
 RNA as Viral Genetic Material
• The broadest variety of RNA genomes is
found among viruses are those that infect
animals.
• There are three types of single stranded
RNA genomes
• The genome of class IV can directly serve
as mRNA and can be translated into viral
protein immediately after infection
 RETROVIRUSES
• Most complicated
• Genetic information flows
in the reverse direction
• Have the enzyme reverse
transcriptase
– Transcribes DNA from an
RNA template
• The newly made DNA than
integrates as a provirus
into the nucleus of the
animal cell
• The host’s RNA
polymerase transcribes the
virual DNA into RNA
molecules.
 Viral Diseases in Animals
• The damage caused by a viral disease depends on
the ability of the tissue infected to regenerate by
cell division.
– Cold virus – we recover from
– Poliovirus - attacks
• Vaccines are harmless variants of pathogenic
microbes that stimulate the immune system to
defenses against the pathogen.
Multiplication of Animal Viruses
• Attachment: Viruses attach to cell
membrane
• Penetration by endocytosis or fusion
• Uncoating by viral or host enzymes
• Biosynthesis: Production of nucleic acid
and proteins
• Maturation: Nucleic acid and capsid
proteins assemble
• Release by budding (enveloped viruses) or
 Attachment, Penetration,
Uncoating
• By pinocytosis

Figure 13.14a
 Attachment, Penetration,
Uncoating
• By fusion

Figure 13.14b
Budding of an Enveloped Virus

Figure 13.20
Budding of an Enveloped Virus

Figure 13.20
Multiplication of DNA Virus

Figure 13.15
Sense Strand (+ Strand) RNA
Virus

Figure 13.17a
Antisense Strand (– Strand) RNA Virus

Figure 13.17b
Double-Stranded RNA Virus

Figure 13.17c
Multiplication of RNA-Containing Viruses

Figure 13.17
Multiplication of a Retrovirus

Figure 13.19
• The link between viral infection and the
symptoms it produces is often obscure.
– Some viruses damage or kill cells by triggering the
release of hydrolytic enzymes from lysosomes.
– Some viruses cause the infected cell to produce
toxins that lead to disease symptoms.
– Other have molecular components, such as envelope
proteins, that are toxic.
• In some cases, viral damage is easily repaired
(respiratory epithelium after a cold), but in
others, infection causes permanent damage
(nerve cells after polio).
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• The first vaccine was developed in the late 1700s
by Edward Jenner to fight smallpox.
– Jenner learned from his patients that milkmaids who
had contracted cowpox, a milder disease that usually
infects cows, were resistant to smallpox.
– In his famous experiment in 1796, Jenner infected a
farmboy with cowpox, acquired from the sore of a
milkmaid with the disease.
– When exposed to smallpox, the boy resisted the
disease.
– Because of their similarities, vaccination with the
cowpox virus sensitizes the immune system to react
vigorously if exposed to actual smallpox virus.
• Effective vaccines against many other viruses
exist.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• Vaccines can help prevent viral infections, but
they can do little to cure most viral infection
once they occur.
• Antibiotics which can kill bacteria by inhibiting
enzyme or processes specific to bacteria are
powerless again viruses, which have few or no
enzymes of their own.
• Some recently-developed drugs do combat some
viruses, mostly by interfering with viral nucleic
acid synthesis.
– AZT interferes with reverse transcriptase of HIV.
– Acyclovir inhibits herpes virus DNA synthesis.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
 6. Plant viruses are serious
agricultural pests
• Plant viruses can stunt plant growth and diminish
crop yields.
• Most are RNA viruses with rod-shaped capsids
produced by a spiral of capsomeres.

Fig. 18.9a
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
 Plant Viruses and Viroids
• Plant viruses:
Enter through
wounds or via
insects
• Viroids:
Infectious
RNA; e.g.,
potato spindle
tuber disease

Figure 13.23
7. Viroids and prions are infectious
agents even simpler than viruses
• Viroids, smaller and simpler than even viruses,
consist of tiny molecules of naked circular RNA
that infect plants.
• Their several hundred nucleotides do not encode
for proteins but can be replicated by the host’s
cellular enzymes.
• These RNA molecules can disrupt plant
metabolism and stunt plant growth, perhaps by
causing errors in the regulatory systems that
control plant growth.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
 Prions
• Proteinaceous Infectious particle
• Inherited and transmissible by ingestion,
transplant, and surgical instruments
– Spongiform encephalopathies: Sheep scrapie,
Creutzfeldt-Jakob disease, Gerstmann-
Sträussler-Scheinker syndrome, fatal familial
insomnia, mad cow disease
 Prions
• PrPC: Normal cellular prion protein, on cell
surface
• PrPSc: Scrapie protein; accumulates in brain
cells, forming plaques
How a Protein Can Be Infectious

Figure 13.22
 8. Viruses may have evolved from
other mobile genetic elements
• Viruses are in the semantic fog between life and
nonlife.
• An isolated virus is biologically inert and yet it
has a genetic program written in the universal
language of life.
• Although viruses are obligate intracellular
parasites that cannot reproduce independently, it
is hard to deny their evolutionary connection to
the living world.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• Because viruses depend on cells for their own
propagation, it is reasonable to assume that they
evolved after the first cells appeared.
• Most molecular biologists favor the hypothesis
that viruses originated from fragments of cellular
nucleic acids that could move from one cell to
another.
– A viral genome usually has more in common with the
genome of its host than with those of viruses
infecting other hosts.
– Perhaps the earliest viruses were naked bits of nucleic
acids that passed between cells via injured cell
surfaces.
– The evolution of capsid genes may have facilitated
Copyrightthe
© 2002infection ofpublishing
Pearson Education, Inc., undamaged cells.
as Benjamin Cummings
• Candidates for the original sources of viral
genomes include plasmids and transposons.
– Plasmids are small, circular DNA molecules that are
separate from chromosomes.
– Plasmids, found in bacteria and in the eukaryote
yeast, can replicate independently of the rest of the
cell and are occasionally be transferred between cells.
– Transposons are DNA segments that can move from
one location to another within a cell’s genome.
• Both plasmids and transposons are mobile
genetic elements.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

• In recent years, several very dangerous
“emergent viruses” have risen to prominence.
– HIV, the AIDS virus, seemed to appear suddenly in
the early 1980s.
– Each year new strains of influenza virus cause
millions to miss work or class, and deaths are not
uncommon.
– The deadly Ebola
virus has caused
hemorrhagic fevers
in central Africa
periodically since
1976.
Fig. 18.8a

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

 Cancer
• Activated oncogenes transform normal cells
into cancerous cells
• Transformed cells have increased growth,
loss of contact inhibition, tumor-specific
transplant antigens, and T antigens
• The genetic material of oncogenic viruses
becomes integrated into the host cell's DNA
 Oncogenic Viruses
• Oncogenic DNA • Oncogenic RNA
viruses viruses
– Adenoviridae – Retroviridae
– Herpesviridae – Viral RNA is
– Poxviridae transcribed to DNA,
– Papovaviridae which can integrate
into host DNA
– Hepadnaviridae
– HTLV-1
– HTLV-2
 Parvoviridae
• Single-stranded
DNA, nonenveloped
viruses
– Fifth disease
– Anemia in
immunocompromise
d patients

Table 13.2
 Adenoviridae
• Double-stranded DNA, nonenveloped viruses
– Respiratory infections in humans
– Tumors in animals

Figure 13.16a
 Papovaviridae
• Double-stranded DNA,
nonenveloped viruses
– Papillomavirus
• Human wart virus
– Polyomavirus
• Cause tumors; some cause
cancer

Table 13.2
 Poxviridae
• Double-stranded DNA, enveloped
viruses
– Orthopoxvirus (vaccinia
and smallpox viruses)
– Molluscipoxvirus
– Smallpox
– Molluscum
contagiosum
– Cowpox

Figure 13.5b
 Herpesviridae
• Double-stranded DNA,
enveloped viruses
– Simplexvirus (HHV-1
and HHV-2)
– Varicellovirus (HHV-3)
– Lymphocryptovirus
(HHV-4)
– Cytomegalovirus (HHV-
5)
– Roseolovirus (HHV-6)
– HHV-7 Figure 13.16b
 Hepadnaviridae
• Double-
stranded DNA,
enveloped
viruses
– Hepatitis B
virus
– Use reverse
transcriptase

Figure 25.15
 Picornaviridae
• Single-stranded
RNA, + strand,
nonenveloped
– Enterovirus
• Poliovirus and
coxsackievirus
– Rhinovirus
– Hepatitis A virus

Table 13.2
 Caliciviridae
• Single-stranded
RNA, + strand,
nonenveloped
– Hepatitis E virus
– Norovirus causes
gastroenteritis

Table 13.2
 Togaviridae
• Single-stranded
RNA, + strand,
enveloped
– Alphavirus
• Transmitted by
arthropods; includes
EEE and WEE
– Rubivirus (rubella
virus)

Table 13.2
 Flaviviridae
• Single-stranded
RNA, + strand,
enveloped
– Arboviruses can
replicate in
arthropods; include
yellow fever, dengue,
SLE, and West Nile
viruses
– Hepatitis C virus

Clinical Focus, p. 223

 Coronaviridae
• Single-stranded
RNA, + strand,
enveloped
– Upper respiratory
infections
– Coronavirus
– SARS

Table 13.2
 Rhabdoviridae
• Single-stranded
RNA, – strand,
one RNA strand
– Vesiculovirus
– Lyssavirus
(rabies virus)
– Cause numerous
animal diseases

Figure 13.18a
 Filoviridae
• Single-stranded
RNA, – strand,
one RNA strand
– Filovirus
– Enveloped,
helical viruses
– Ebola and
Marburg viruses

Figure 23.21
 Paramyxoviridae
• Single-stranded
RNA, – strand, one
RNA strand
– Paramyxovirus
– Morbillivirus
– Parainfluenza
– Mumps
– Newcastle disease
(chickens)

Table 13.2
 Deltaviridae
• Single-stranded RNA,
– strand, one RNA
strand
– Hepatitis D virus
– Depends on coinfection
with hepadnavirus

Table 13.2
 Orthomyxoviridae
• Single-stranded RNA,
– strand, multiple RNA
strands
– Envelope spikes can
agglutinate RBCs
– Influenzavirus (influenza
viruses A and B)
– Influenza C virus

Table 13.2
Avian Influenza

Clinical Focus, p. 371

 Bunyaviridae
• Single-stranded RNA, –
strand, multiple RNA
strands
– Bunyavirus (CE virus)
– Hantavirus

Table 13.2
 Arenaviridae
• Single-stranded RNA,
– strand, multiple RNA
strands
– Helical capsids contain
RNA-containing
granules
– Lymphocytic
choriomeningitis
– VEE and Lassa fever

Table 13.2
 Retroviridae
• Single-stranded
RNA, 2 RNA
strands,
produce DNA
– Use reverse
transcriptase to
produce DNA from
viral genome
– Lentivirus (HIV)
– Oncogenic viruses
• Includes all RNA
Figure 19.13
tumor viruses
 Reoviridae
• Double-stranded RNA,
nonenveloped
– Reovirus (respiratory
enteric orphan)
– Rotavirus (mild
respiratory infections and
gastroenteritis)
– Colorado tick fever

Table 13.2
Q&A
• Researchers
converted skin cells
into embryonic stem
cells. They first
inserted RNA
complementary for
four embryonic
genes into a virus;
the resulting provirus
inserted the genes
into the skin cells’
DNA. What virus
More than 300 viruses are known to infect humans and to cause as many as 50 different syndromes.

Steps in Viral Pathogenesis

A- Viral entry and primary replication.
B- Viral Spread and Cell Tropism.
C- Cell Injury and Clinical Illness.
D- Recovery From Infection.
E- Virus Shedding.

Host Immune Response

1- Both humeral and cellular immunity are involved in control of viral infection.
2- Mononuclear cells and lymphocytes are involved in viral infection.
3- The capsid serves as the targetfor the immune response.
4- Cytotoxic T lymphocytes lyse virus infected cells.
5- Secretory IgA antibody is important against viral infections of the respiratory or gastrointestinal tract.
6- Among the nonimmune responses is the induction of interferone.
1- Some viruses infect and damage cells of the immune system(AIDS).
2- Development of pathologic changes and clinical illness.
3- Immunopathologic disorder due to vaccine immunization.
4- Development of autoantibodies.
Viruses have a variety of ways that serve to suppress or evade the host immune response
and thus avoid eradication:
1- Oftentimes the viral proteins involved in modulating the host response are not essential
for the growth of the virus.
2- Some viruses infect cells of the immune system and abrogate their function(AIDS).
3- They may infect neurons that express little or no class 1 MHC(herpesviruses).
4- Form proteins that inhibit MHC function(adenoviruses).
5- Viruses may mutate and change the antigenic sites on virion proteins(influenza virus).
6- Regulate the level of viral surface proteins(herpesvirus).
Viral infections are usually self-limiting. Sometimes, however, the virus persists
for long periods of time in the host. Long-term virus-host interaction may take
several forms:
1- Chronic infections.
2- Latent infections.
3- Inapparent or subclinical infections.

Acute Viral Respiratory Infections.

Viral Infections of the Gastrointestinal Tract.
Viral skin Infections
Viral Infections of the CNS
Congenital Viral Infections.
Rubella, CMV, Herpes simplex, Varicella-zoster, HBV, Enterovirus, HIV, Parvovirus B19
Latent and Persistent Viral
Infections

Figure 13.21
 Latent Viral Infections
• Virus remains in
asymptomatic
host cell for
long periods
– Cold sores,
shingles

Figure 13.21
 Persistent Viral Infections
• Disease
processes
occurs over a
long period;
generally is
fatal
– Subacute
sclerosing
panencephaliti
s (measles
virus)
Figure 13.21
As bacteria and protozoa do not relay on host cellular machinery for replication, so processes
specific to these organisms provide ready targets for the development of antibacterial and
antiprotozoal drugs. However, because viruses are obligate intracellular parasites, antiviral drugs
must be capable of selectively inhibiting viral functions without damaging the host, making the
development of such drugs very difficult. Furthermore an ideal drug would reduce disease
symptoms without modifying the viral infection so much as to prevent an immune response in the
host. There is a need for antiviral drugs active against viruses for which vaccines are not available or
not highly effective.
A- Nucleoside analogs.
B- Nucleotide analogs.
C- Nonnucleoside Reverse transcriptase inhibitors.
D- Protease inhibitors: Saquinavir.
E- Other types: Amentadine, Rimantadine, Foscarent, Methisazone.
F- Interferons

Properties
Synthesis
Antiviral activity and other biologic effects.
Clinical studies.