Transcript Prevention and treatment of viral infections1.75 MB

Definition and Properties of a Virus
•Viruses are filterable agents.
•Viruses are obligate intracellular parasites.
•Viruses cannot make energy or proteins independently of a host cell.
•Viral genomes may be RNA or DNA but not both.
•Viruses have a naked capsid or an envelope morphology.
•Viral components are assembled and do not replicate by "division."
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Consequences of Viral Properties
Viruses are not living.
Viruses must be infectious to endure in nature.
Viruses must be able to use host cell processes
to produce their components (viral messenger
RNA, protein, and identical copies of the
genome).
• Viruses must encode any required processes
not provided by the cell.
• Viral components must self-assemble.
• Means of Classification and Naming of Viruses
• Structure: size, morphology, and nucleic acid (e.g.,
picornavirus [small RNA], togavirus)
• Biochemical characteristics: structure and mode of
replication*
• Disease: encephalitis and hepatitis viruses, for example
• Means of transmission: arbovirus spread by insects, for
example
• Host cell (host range): animal (human, mouse, bird),
plant, bacteria
• Tissue or organ (tropism): adenovirus and enterovirus,
for example
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Picornavirus
Togavirus
Retrovirus
Poxvirus
Adenovirus
Reoviruses
Norwalk virus
Coxsackie virus
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The DNA viruses and their morphology. The viral families are determined by
the structure of the genome and the morphology of the virion
The RNA viruses, their genome structure, and their morphology. The viral
families are determined by the structure of the genome and the morphology of
the virion. E, enveloped; N, naked capsid.
Viruses
• nm
• Parvovirus 18nm
• Poxvirus 300nm
• Families of DNA Viruses and Some Important Members
Family
Members
• POXVIRIDAE
Smallpox virus, vaccinia virus, monkeypox,
molluscum contagiosum
• Herpesviridae
Herpes simplex virus types 1 and 2, varicellazoster virus, Epstein-Barr virus, CMV, human
herpesviruses 6, 7, and 8
• Adenoviridae
Adenovirus
• Papilloma viridae
Papilloma virus
• Polyoma viridae
JC virus, BK virus,SV40
• Hepadnaviridae
Hepatitis B virus
• Parvoviridae
Parvovirus B19, adeno-associated virus
*The italicized virus is the important, or prototype, virus for the
family.
Steps in Viral Replication
• Recognition of the target cell
• Attachment
• Penetration
• Uncoating
• Macromolecular synthesis
– Early messenger RNA (mRNA) and nonstructural protein synthesis:
genes for enzymes and nucleic acid-binding proteins
– Replication of genome
– Late mRNA and structural protein synthesis
– Post-translational modification of protein
• Assembly of virus
• Budding of enveloped viruses
• Release of virus
• Examples of Viral Attachment ProteinsVirus
Family
Virus
VAP
• Picornaviridae
Rhinovirus
VP1-VP2-VP3
• Adenoviridae
Adenovirus
Fiberprotein
• Reoviridae
Reovirus
σ1
Rotavirus
VP7
• Togaviridae
Semliki Forest vE1-E2-E3 complex
Rhabdoviridae
Rabies virus
G protein
• Orthomyxoviridae
Influenza A
HA
• Paramyxoviridae
Measles virus HA
• Herpesviridae
Epstein-Barr v gp350 and gp220
• Retroviridae
Murine leukemia vgp7
Human immunodeficiency virusgp120
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gp, glycoprotein; HA, hemagglutinin; VAP, viral attachment protein.
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Examples of Viral Receptors
Virus
Target Cell
Epstein-Barr virus
B cell
HIV
Helper T cell
Rhinovirus
Epithelial cells
protein)
Poliovirus
Epithelial cells
Herpes simplex virus
Many cells
Rabies virus
Neuron
adhesion molecule)
Influenza A virus
Epithelial cells
B19 parvovirus
Erythroid precursors
*Other receptors for these viruses may also exist.
ICAM-1, Intercellular adhesion molecule.
Receptor*
C3d complement receptor CR2 (CD21)
CD4 molecule and chemokine coreceptor
ICAM-1 (immunoglobulin superfamily
Immunoglobulin superfamily protein
Herpesvirus entry mediator (HVEA),nectin-1
Acetylcholine receptor, NCAM (neural cell
Sialic acid
Erythrocyte P antigen (globoside)
Mechanisms of Viral Pathogenesis
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Determinants of Viral Disease
Nature of the Disease
Target tissue
Portal of entry of virus
Access of virus to target tissue
Tissue tropism of virus
Permissiveness of cells for viral replication
Viral pathogen (strain)
Severity of Disease
Cytopathic ability of virus
Immune status
Competence of the immune system
Prior immunity to the virus
Immunopathology
Virus inoculum size
Length of time before resolution of infection
General health of the person
Nutrition
Other diseases influencing immune status
Genetic makeup of the person
Age
The stages of viral infection. The
virus is released from one person,
is acquired by another, replicates,
and initiates a primary infection at
the site of acquisition. Depending
on the virus, it may then spread to
other body sites and finally to a
target tissue characteristic of the
disease. B, The cycle starts with
acquisition, as indicated, and
proceeds until the release of new
virus. The thickness of the arrow
denotes the degree to which the
original virus inoculum is amplified
on replication. The boxes indicate
a site or cause of symptoms. C,
Time course of viral infection. The
time course of symptoms and the
immune response correlate with
the stage of viral infection and
depend on whether the virus
causes symptoms at the primary
site or only after dissemination to
another (secondary) site. CMV,
cytomegalovirus; HBV, hepatitis B
virus; HIV, human
immunodeficiency virus.
Mechanisms of Viral Pathogenesis
• Failed infection (abortive infection).
• Cell death (lytic infection).
• Replication without cell death (persistent
infection).
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Determinants of Viral Pathogenesis
Interaction of Virus with Target Tissue
Access of virus to target tissue
Stability of virus in the body
– Temperature
– Acid and bile of the gastrointestinal tract
Ability to cross skin or mucous epithelial cells (e.g., cross the gastrointestinal tract into the bloodstream)
Ability to establish viremia
Ability to spread through the reticuloendothelial system
Target tissue
– Specificity of viral attachment proteins
– Tissue-specific expression of receptors
Cytopathologic Activity of the Virus
Efficiency of viral replication in the cell
– Optimum temperature for replication
– Permissiveness of cell for replication
Cytotoxic viral proteins
Inhibition of cell's macromolecular synthesis
Accumulation of viral proteins and structures (inclusion bodies)
Altered cell metabolism (e.g., cell immortalization)
Host Protective Responses
Antigen-nonspecific antiviral responses
– Interferon
– Natural killer cells and macrophages
Antigen-specific immune responses
– T-cell responses
– Antibody responses
Viral mechanisms of escape of immune responses
Immunopathology
Interferon: flulike systemic symptoms
T-cell responses: delayed-type hypersensitivity
Antibody: complement, antibody-dependent cellular cytotoxicity, immune complexes
Other inflammatory responses