Transcript Introduction to Virology David C. Ansardi, Ph.D. Department of Cell

Introduction to Virology
Casey D. Morrow, Ph.D.
Department of Cell Biology
[email protected]
•Viral replication: How viruses exploit cells
to make new viruses
•Viral pathogenesis: How virus replication
causes disease and how viruses
escape/interact with the immune system
The DNA -> RNA -> Protein Pathway
RNA Polymerase =
enzyme that makes
mRNA from the
DNA gene template
http://www.bioteach.ubc.ca/MolecularBiology/AMonksFlourishingGarden/
Characteristics of Viruses
•“Filterable agents” – Pass through filters that capture bacteria
•Obligate intracellular parasites
•Minimal genetic information, efficient
•Rely on host cell machinery to fulfill replication cycle
•Assembled from building blocks encoded by the virus (don’t
divide like cells)
•Absolutely require host cell for replication to produce proteins
required to synthesize new viral genomes and the building
blocks of the virus structure
For a Virus to be Successful:
•Capable of transmission through potentially harsh
environmental conditions
•Traverse skin or other barriers of the host
•Must adapt to the biochemical machinery of the host
cell for replication
•Escape elimination by the host immune response
Basic Components of a
Virion
Virus Classification
•Size
•Morphology
•Genome Type (DNA or RNA)
•Means of Replication
Relative Sizes of Viruses
General Structure of
Viruses
Genome Contents of Viruses
•RNA
•Single-strand
•Double-strand
•Linear
•segmented
•DNA
•Double-strand
•Single-strand
•Linear
•Circular
http://gsbs.utmb.edu/microbook/images/fig41_6.JPG
Naked vs. Enveloped
Viruses
•Naked Capsids
•Withstand harsh environmental
conditions
•Resistant to drying, acids, detergents
•Many are transmitted fecal-oral route
•Enveloped Viruses
•Can’t dry out
•Not stable in acid
•General must remain in body fluids
(respiratory, blood)
http://www.cat.cc.md.us/courses/bio141/lecguide/unit2/viruses/images/u2fig
2b.jpg
http://www.tarvacin.com/media/gif/EnvelopedVirusStructure.gif
Icosahedral Capsid
Assembly
Examples of Icosahedral
Capsids
1.
Equine Herpesvirus Nucleocapsid
2.
Simian Rotavirus
3.
Reovirus type 1 virion
4.
Intermediate partice: Reovirus
5.
Inner core particle (Reovirus)
6.
Human Papillomavirus type 19
7.
Mouse Polyomavirus
8.
Cauliflower Mosaic Virus
General Enveloped Virus
Structure
HIV
Influenza
http://www.schoolscience.co.uk/content/5/biology/mrc/hiv/page2.html
Example Envelope Glycoprotein:
Influenza Hemagglutinin
Steps of Virus Replication
Cycle
Recognition of Cells and
Attachment
HIV
Sialic acid: bound by Influenza virus
Steps of Virus Replication
Cycle
Cell Entry:
Naked Viruses:
Typically
endocytosis
Enveloped Viruses:
Typically cell fusion
Synthesis of New Viral
Components
•Viral Nucleic Acids
•mRNA’s encoding viral proteins
•New viral genomes for encapsidation into new virions (viral
particles)
•Viral Proteins
•Enzymes and other proteins required for viral transcription and
genome replication
•Structural proteins (capsid proteins, viral glycoproteins)
The DNA -> RNA -> Protein Pathway
RNA Polymerase =
enzyme that makes
mRNA from the
DNA gene template
http://www.bioteach.ubc.ca/MolecularBiology/AMonksFlourishingGarden/
DNA Virus Transcription
•Generally use the host cell’s DNA-dependent RNA
Polymerase II to make mRNA’s
•Generally the DNA genomes go to the nucleus (some
integrate into chromosomal DNA)
•One exception: Poxvirus family – Replicates only in the
cytoplasm of cell so can’t use host cell’s RNA Polymerase
II; instead, makes its own enzymes for transcription of
mRNA’s
RNA Virus Transcription
•Many replicate entirely in the cytoplasm of the cell
•Must encode their own enzymes (RNA-dependent RNA
polymerases) for transcription of mRNA and to replicate their
full-length RNA genomes
•REASON: The host cell has no enzymes for generating new
viral RNA genomes using an RNA template
•PLUS-STRAND RNA VIRUSES: Genomes same sense as mRNA
•MINUS-STRAND RNA VIRUSES: Genomes opposite sense as
mRNA
Replication of Viral Genomes
•DNA Viruses:
•DNA-dependent DNA polymerases to make new DNA copies
from DNA templates
•Some use cellular DNA polymerases
•Others encode their own DNA polymerases
•RNA Viruses:
•Use RNA-dependent RNA polymerases to make new RNA copies
from RNA templates
•Encoded by the virus
•Plus-strand versus minus-strand
•Retroviruses (example: HIV):
•Genome in the viral particle is single-strand RNA
•Packages Reverse Transcriptase
•RNA  DNA  Integrated into chromosomal DNA
•New viral RNA genomes transcribed in the nucleus by host cell
polymerase
Viral Protein Synthesis
•All viruses depend on host cell translation machinery
(ribosomes, tRNA, post-translational modifications) to
generate viral proteins from mRNA templates
•Different strategies for compactness/efficiency:
•Separate mRNA’s for each viral protein
•Polyprotein strategy
•Multiple proteins encoded on one mRNA
•Individual proteins are derived from polyprotein
by enzymatic cleavages catalyzed by proteases
Polyprotein Strategy
Assembly and Release
•Enveloped Viruses:
typically exit by
budding from the cell
•Naked viruses:
typically exit through
cell lysis
Lytic Virus Growth Curve
Viral Budding from Cell
Membrane
HIV budding from a cultured lymphocyte
Budding Influenza
Virus
http://www.itech.pjc.edu/fduncan/mcb1000/micc6ppt_files/slide0004_image012.jpg
http://en.wikipedia.org/wiki/AIDS http://www.med.wayne.edu/immunology/department/roberts2.html
Viral Pathogenesis
•Interaction between the virus and the host
•General Steps:
•Entry into the body (ex. Fecal-Oral, Inhalation)
•Primary Site of Replication
•Viremia
•Secondary Site of Replication in target tissues
Example: Ebola
Primary
Target
Secondary
Targets
Outcomes of Virus Infection
at the Cellular Level
•Failed infection (abortive)
•Cell death:
•Lytic viruses
•Apoptosis (programmed cell death)
•Infection without cell death
•Chronic infection: no cell lysis, new viruses are produced
•Latent infection: limited production of viral components; no new viruses
produced
•Cellular properties may change later resulting in viral production (ex.
Herpes Simplex Virus)
•Transformation: Virus infection results in cell immortalization (conversion to a
tumor cell)
•Oncogenic viruses
Host Defenses Against
Viruses
•Natural Barriers of the Body (ex. Skin)
•Innate Immune Defenses (not antigen dependent)
•Interferon response
•Macrophages
•Dendritic cells
•Natural Killer Cells
•Antigen-specific immune responses
•Antibodies
•Helper T-cells
•Cell-mediated immunity
•Recognition of virus-infected cells
•Lysis of infected cells
Viral Strategies to Evade Host
Defenses
•Preventing interferon action:
•Presence of double-stranded RNA in cell causes interferon response
•Shuts down cellular translation (suspended animation)
•Degradation of viral RNA
•Changing viral antigens
•High error-rate in many viral polymerases
•Allows rapid change of protein sequences and, therefore, antigenic
characteristics
•Cell-to-cell spread: Evade antibodies
•Suppression of antigen presentation and lymphocyte function (hide from
immune system)
Viral immunopathogenesis
Immunopathogenesis
Immune Mediators
Examples
Flulike symptoms
Interferon, cytokines
Respiratory viruses, arboviruses (viremiainducing viruses)
Delayed-type hypersensitivity
and inflammation
T cells, macrophages, and
polymorphonuclear leukocytes
Enveloped viruses
Immune complex disease
Antibody, complement
Hepatitis B virus, rubella
Hemorrhagic disease
T cell, antibody, complement
Yellow fever, dengue, Lassa fever, Ebola viruses
Postinfection cytolysis
T cells
Enveloped viruses (e.g., postmeasles
encephalitis)
Immunosuppression
-
Human immunodeficiency virus,
cytomegalovirus, measles virus, influenza
virus