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GENERAL PROPERTIES OF
VIRUSES
Smallest infectious agents (20nm-300nm
in diameter)
Contain only one kind of nucleic acid
(RNA or DNA) as their genome
Nucleic acid is encased in a protein shell
which may be surrounded by a lipdcontaining membrane
VIRION entire infectious unit
Inert in the extracellular environment;
replicate only in living cells
GENERAL PROPERTIES OF
VIRUSES
Viral nucleic acid contains information
necessary for programming the
infected host cell to synthesize virusspecific macromolecules required for
the production of viral progeny
During the replicative cycle, numerous
copies of viral nucleic acid and coat
proteins are produced
GENERAL PROPERTIES OF
VIRUSES
Coat proteins assemble together to
form the capsid (encases and
stabilizes the viral nucleic acid against
the extracellular environment;
facilitates the attachment and
penetration by the virus upon contact
with new susceptible cells)
GENERAL PROPERTIES OF
VIRUSES
Rich in diversity viruses vary greatly
in structure, genome organization
and expression, strategies of
replication and transmission
Host range maybe broad or extremely
limited
Known to infect unicellular organisms
such as mycoplasmas, bacteria and
algae and all higher plants and
animals
EVOLUTIONARY ORIGIN OF
VIRUSES
Origin of viruses not known
2 theories:
1. Viruses may be derived from
DNA or RNA nucleic acid components of
host cells that became able to replicate
autonomously and evolve
independently
2. Viruses may be degenerate
forms of intracellular parasites
CLASSIFICATION OF VIRUSES
BASIS OF CLASSIFICATION
1. Virion morphology, size, shape, type of
symmetry, presence or absence of peplomers,
and presence or absence of membranes
2. Virus genome properties, including type of
nucleic acid (DNA or RNA), size of genome (kb
or kbp), strandedness (single or double),
whether linear or circular, sense (positive,
negative, ambisense), segments (number,
size), nucleotide sequence, G + C content, and
presence of special features [repetitive
elements, isomerization, 5'-terminal cap, 5'terminal covalently linked protein, 3'-terminal
poly(A) tract]
CLASSIFICATION OF VIRUSES
BASIS OF CLASSIFICATION
3. Genome organization and replication,
including gene order, number and position of
of open reading frames, strategy of replication
(patterns of transcription, translation), and
cellular sites (accumulation of proteins, virion
assembly, virion release)
4. Virus protein properties, number, size, and
functional activities of structural and
nonstructural proteins, AA sequence,
modifications (glycosylation, phosphorylation,
myristylation), and special functional activities
(transcriptase, reverse transcriptase,
neuraminidase, fusion activities)
CLASSIFICATION OF VIRUSES
BASIS OF CLASSIFICATION
5. Antigenic properties
DNA VIRUSES
A. Parvoviruses
Human parvovirus B19 aplastic
crisis, fifth disease, fetal death
B. Anelloviruses
C. Polyomaviruses
JC virus progressive multifocal
leukoencephalopathy
BK virus nephropathy in transplant
recipients
Merkel cell virus - Merkel cell skin CA
DNA VIRUSES
D. Papillomaviruses
wart viruses
E. Adenoviruses- acute respiratory
diseases, conjuctivitis ,
gastroenteritis
F. Hepadnaviruses acute and
chronic hepatitis
DNA VIRUSES
G. Herpesviruses
Herpes simplex type 1 & 2 (oral &
genital lesions)
Varicella-zoster virus (chickenpox &
shingles)
Cytomegalovirus
Epstein-Barr virus (infectious
mononucleosis, assoc. with human neoplasms)
Human herpesvirus 6 & 7 (T
lymphocytic)
Human herpesvirus 8 (Kaposi sarcoma)
DNA VIRUSES
H. Poxviruses
smallpox
vaccinia
molluscum contangiosum
cowpox
monkeypox
RNA VIRUSES
A. Picornaviruses
Enteroviruses (polioviruses,
coxsackieviruses, and echoviruses,
rhinoviruses (common colds) and
hepatoviruses (Hepatitis A)
B. Astroviruses- gastroenteritis
C. Caliciviruses
Noroviruses (Norwalk virus)
epidemic acute gastroenteritis
RNA VIRUSES
D. Hepeviruses
Human Hepatitis E virus
E. Picobirnaviruses
F. Reoviruses
Rotaviruses (wheel-shaped appearance;
gastroenteritis)
G. Arboviruses and Rodent-Borne Viruses
Dengue Virus
Yellow fever virus
West Nile fever virus
Encephalitis virus
RNA VIRUSES
H. Togaviruses
Rubella virus
I. Flaviviruses
Hepatitis C virus
J. Arenaviruses
K. Coronaviruses
colds
SARS (severe acute respiratory
syndrome)
RNA VIRUSES
L. Retroviruses
AIDS
M. Orthomyxoviruses
Influenza viruses
N. Bunyaviruses
O. Bornaviruses
P. Rhabdoviruses
Rabies virus
Q. Paramyxoviruses
Mumps, measles, parainfluenza,
metapneumo & respiratory syncytial viruses
RNA VIRUSES
R. Filoviruses
Marburg virus
Ebola virus
severe hemorrhagic
fever in Africa
CHEMICAL COMPOSITION OF
VIRUSES
VIRAL PROTEIN
Facilitate transfer of the viral nucleic
acid from one host to another
Serve to protect the viral genome
against inactivation by nucleases
Participate in the attachment of the
virus particle to a susceptible cell
Provide structural symmetry of the
virus particle
Determines the antigenic
characteristics of the virus
Some viruses carry enzymes (which
are proteins) inside the virions
CHEMICAL COMPOSITION OF
VIRUSES
VIRAL NUCLEIC ACID
Viruses contain a SINGLE kind of
nucleic acid either DNA or RNA
that encodes the genetic information
necessary for replication of the virus.
The genome may be single-stranded
or double-stranded, circular or
linear, and segmented or
nonsegmented.
The type of nucleic acid, its
strandedness, and its size are major
characteristics used for classifying
viruses into families
CHEMICAL COMPOSITION OF
VIRUSES
VIRAL NUCLEIC ACID
Viral RNAs exist in several forms
may be a single linear molecule
(picornaviruses)
several segments of RNA that may
be loosely associated within the
virion (orthomyxoviruses)
The isolated RNA of viruses with
positive-sense genomes (ie,
picornaviruses, togaviruses) is
infectious, and the molecule
functions as an mRNA within the
infected cell
CHEMICAL COMPOSITION OF
VIRUSES
VIRAL NUCLEIC ACID
The isolated RNA of the negativesense RNA viruses, such as
rhabdoviruses and orthomyxoviruses,
is not infectious
The sequence and composition of
nucleotides of each viral nucleic acid
are distinctive. Many viral genomes
have been sequenced. The sequences
can reveal genetic relationships
among isolates
CHEMICAL COMPOSITION OF
VIRUSES
VIRAL NUCLEIC ACID
Viral nucleic acid may be
characterized by its G + C content.
DNA viral genomes can be analyzed
and compared using restriction
endonucleases, enzymes that cleave
DNA at specific nucleotide
sequences; each genome will yield a
characteristic pattern of DNA
fragments after cleavage with a
particular enzyme
CHEMICAL COMPOSITION OF
VIRUSES
VIRAL LIPID ENVELOPES
A number of different viruses contain
lipid envelopes as part of their
structure
The lipid is acquired when the viral
nucleocapsid buds through a cellular
membrane in the course of maturation
CHEMICAL COMPOSITION OF
VIRUSES
VIRAL GLYCOPROTEINS
Viral envelopes contain glycoproteins
In contrast to the lipids in viral
membranes, which are derived from
the host cell, the envelope
glycoproteins are virus-encoded.
the sugars added to viral glycoproteins
often reflect the host cell in which the
virus is grown
CHEMICAL COMPOSITION OF
VIRUSES
VIRAL GLYCOPROTEINS
It is the surface glycoproteins of an
enveloped virus that attach the virus
particle to a target cell by interacting
with a cellular receptor
often involved in the membrane fusion
step of infection
important viral antigens
CULTIVATION OF VIRUSES
Many viruses can be grown in cell cultures
or in fertile eggs under strictly controlled
conditions
Growth of virus in animals is still used for
the primary isolation of certain viruses and
for studies of the pathogenesis of viral
diseases and of viral oncogenesis.
No apparent
effect
Viral disease
Some harmful abnormality that results from viral
infection of the host organism.
Clinical disease
consists of overt signs and symptoms.
Syndrome
a specific group of signs and symptoms.
Inapparent (subclinical)
Viral infections that fail to produce any symptoms in
the host.
Important Features
of Acute Viral Diseases
Local Infections
Systemic Infections
Respiratory (rhinovirus)
Measles
Site of pathology
Portal of entry
Distant site
Incubation period
Relatively short
Relatively long
Viremia
Absent
Present
Duration of immunity
Variablemay be short
Usually lifelong
Viral pathogenesis
The interaction of viral and host factors that leads
to disease production.
Common Routes
of Viral Infection in Humans
Route of Entry
Virus Group
Respiratory tract
Parvovirus
Produce Local
Produce Generalized
Symptoms at Portal of Infection Plus Specific
Entry
Organ Disease
B19
Adenovirus
Most types
Herpesvirus
Epstein-Barr virus,
herpes simplex virus
Poxvirus
Picornavirus
Varicella virus
Smallpox virus
Rhinoviruses
Togavirus
Some enteroviruses
Rubella virus
Coronavirus
Most types
Orthomyxovirus
Influenza virus
Paramyxovirus
Parainfluenza viruses,
respiratory syncytial
virus
Common Routes
of Viral Infection in Humans
Route of Entry
Virus Group
Produce Local
Produce Generalized
Symptoms at Portal of Infection Plus Specific
Entry
Organ Disease
Some types
Epstein-Barr virus,
herpes simplex virus
Picornavirus
Reovirus
Cytomegalovirus
Some enteroviruses,
including poliovirus and
hepatitis A virus
Rotaviruses
Common Routes
of Viral Infection in Humans
Route of Entry Virus Group
Produce Local
Symptoms at Portal
of Entry
Skin
Mild trauma
Injection
Bites
Papillomavirus
Most types
Herpesvirus
Poxvirus
Molluscum
contagiosum virus, orf
virus
Hepadnavirus
Hepatitis B
Herpesvirus
Retrovirus
Togavirus
Flavivirus
Rhabdovirus
OR
Recovery mechanisms
Innate immune response
Adaptive immune responses
Antiviral Chemotherapy
Interferons
Viral Vaccines
Limitations:
Antiviral agents must be capable of selectively
inhibiting viral functions without damaging the
host.
Many rounds of virus replication occur during the
incubation period and the virus has spread before
symptoms appear
making a drug relatively ineffective.
Drug
Nucleoside Analog
Mechanism of Action
Acyclovir
Yes
Amantadine
No
Cidofovir
No
Didanosine (ddI)
Yes
Reverse transcriptase
inhibitor
Foscarnet
No
Fuzeon
No
Ganciclovir
Yes
Indinavir
No
HIV-1, HIV-2
Lamivudine (3TC)
Yes
Reverse transcriptase
inhibitor
Nevirapine
No
Reverse transcriptase
inhibitor
HIV-1
Influenza A
HIV-1, HIV-2
Drug
Nucleoside Analog
Mechanism of Action
Ribavirin
Yes
Ritonavir
No
HIV-1, HIV-2
Saquinavir
No
HIV-1, HIV-2
Stavudine (d4T)
Yes
Reverse transcriptase
inhibitor
HIV-1, HIV-2
Trifluridine
Yes
Valacyclovir
Yes
Vidarabine
Yes
Zalcitabine (ddC)
Yes
Reverse transcriptase
inhibitor
Zidovudine (AZT)
Yes
Reverse transcriptase
inhibitor
Saquinavir
The first protease inhibitor to be approved for
treatment of HIV infection.
MOA
Inhibit the viral protease
that is required at the
late stage of the
replicative cycle
Fuzeon
a large peptide
MOA:
Blocks the virus and cellular membrane fusion
step involved in entry of HIV-1 into cells.
Amantadine and
Rimantadine
Foscarnet
(Phosphonoformic
Acid, PFA)
Methisazone
An inhibitor of poxviruses.
It was the first antiviral agent to be described and contributed to the
campaign to eradicate smallpox.
It blocked a late stage in viral replication, resulting in the formation of
immature, noninfectious virus particles.
Alpha
Beta
Gamma
IFN-
IFN-
Former designation
Leukocyte
Fibroblast
Immune interferon
Type designation
Type I
Type I
Type II
20
Lymphocytes
Inducing agent
Viruses; dsRNA
Viruses; dsRNA
Mitogens
Stability at pH 2.0
Stable
Stable
Labile
Glycosylated
No
Yes
Yes
Introns in genes
No
No
Yes
8095%
30%
< 10%
12
166
143
IFNAR
IFNGR
Chromosomal location 21
of IFN receptor genes
21
Dendritic cells
are potent interferon producers;
under the same virus challenge conditions,
dendritic cells can secrete up to 1000x more
interferon than fibroblasts.
IFN-
not produced in response to most viruses but is induced
by mitogen stimulation.
IFN-
produced mainly by lymphocytes, especially T cells
and natural killer (NK) cells.
Dendritic cells
are potent interferon producers;
under the same virus challenge conditions, dendritic
cells can secrete up to 1000x more interferon than
fibroblasts.
Synthesis of several
enzymes believed to be
instrumental in the
development of the
antiviral state.
Interferons are almost always host speciesspecific in function but are not specific for a
given virus.
When interferon is added to cells prior to
infection, there is marked inhibition of viral
replication but nearly normal cell function.
Interferons are extremely potent, so that very
small amounts are required for function.
<50 molecules of interferon per cell are sufficient to
induce the antiviral state.
Killed-Virus Vaccines
Attenuated Live-Virus
Vaccines
Advantages
There is no reversion to
virulence by the vaccine virus
and that vaccines can be
made when no acceptable
attenuated virus is available.
Disadvantages
Extreme care is required in their manufacture to
make certain that no residual live virulent virus is
present in the vaccine.
The immunity conferred is often brief and must be
boosted, which not only involves the logistic
problem of repeatedly reaching the persons in need
of immunization but also has caused concern about
the possible effects (hypersensitivity reactions) of
repeated administration of foreign proteins.
Disadvantages
Parenteral administration of killed-virus
vaccine, even when it stimulates circulating
antibody (IgM, IgG) to satisfactory levels, has
sometimes given limited protection because
local resistance (IgA) is not induced adequately
at the natural portal of entry or primary site of
multiplication of the wild virus infectioneg,
nasopharynx for respiratory viruses, alimentary
tract for poliovirus
Disadvantages
The cell-mediated response to
inactivated vaccines is generally poor.
Some killed-virus vaccines have induced
hypersensitivity to subsequent infection,
perhaps owing to an unbalanced immune
response to viral surface antigens that
fails to mimic infection with natural virus.
Advantage
Act like the natural infection with regard to
their effect on immunity.
They multiply in the host and tend to
stimulate longer-lasting antibody
production, to induce a good cell-mediated
response, and to induce antibody
production and resistance at the portal of
entry.
Disadvantages
The risk of reversion to greater virulence during multiplication
within the vaccinee. Although reversion has not proved to be a
problem in practice, its potential exists.
Unrecognized adventitious agents latently infecting the culture
substrate (eggs, primary cell cultures) may enter the vaccine
stocks. Viruses found in vaccines have included avian leukosis
virus, simian polyomavirus SV40, and simian cytomegalovirus.
The problem of adventitious contaminants may be circumvented
through the use of normal cells serially propagated in culture
(eg, human diploid cell lines) as substrates for cultivation of
vaccine viruses.
Disadvantages
The storage and limited shelf life of attenuated
vaccines present problems, but this can be overcome
in some cases by the use of viral stabilizers (eg, MgCl2
for poliovaccine).
Interference by coinfection with a naturally occurring,
wild-type virus may inhibit replication of the vaccine
virus and decrease its effectiveness. This has been
noted with the vaccine strains of poliovirus, which can
be inhibited by concurrent infections by various
enteroviruses.