Viruses and Prions
Chapter 14
14.1 Structure and Classification of
Animal Viruses
Structure
DNA or RNA genome
Double stranded (ds) or single stranded (ss)
Surrounded by a capsid (protein coat)
The nucleic acid and capsid are termed
nucleocapsid
Some viruses have an envelope
The envelope is a phospholipid bilayer
membrane that was obtained from the cell in
which the virus arose
14.1 Structure and Classification of
Animal Viruses
Viruses are obligate intracellular parasites
They occur in many shapes, some of which
are distinctive
Human
papillomavirus
Rhabdovirus
Ebola virus
14.1 Structure and Classification of
Viral genomesAnimal
exhibit aViruses
range of complexity
Polioviruses: single-stranded RNA virus
Herpesviruses: double-stranded DNA
Retroviruses: diploid single-stranded RNA
Influenza viruses: multiple gene segments of
single-stranded RNA
Genome sizes
Hantaviruses have 3 genes that encode 4 polypeptides
Pox viruses have nearly 200 genes
There are thousands of known viruses (and probably
14.1 Structure and Classification of
Animal Viruses
Virus Classification
Genome structure
Virus particle structure
Presence or absence of an envelope
Nomenclature rule: Viruses are named for the
geographic region in which they are
discovered
14.1 Structure and Classification of
Animal Viruses
Groupings by Transmission Mechanism
Enteric viruses: fecal-oral route
Respiratory viruses: aerosols
Zoonotic agents
Biting
Respiratory route
Sexually-transmitted
14.2 Interactions of Animal Viruses
and Their Hosts
Viruses tend to be species- and cell-specific
Infection is a 9-step process
Attachment
Entry
Targeting to site of viral replication
Uncoating
Nucleic acid replication and protein synthesis
Maturation
Release from cells
Shedding from host
Transmission to other hosts
14.2 Interactions of Animal Viruses
and Their Hosts
Step 1: Attachment
Mediated by cellsurface molecule(s)
and viral spike proteins
HIV gp120 is specific for
CD4
CD4 is principally found on
helper T cells
Occurs by noncovalent
interactions
14.2 Interactions of Animal Viruses
and Their Hosts
Step 2: Entry into the cell
Some viruses fuse with the cell’s plasma
membrane
HIV’s gp41 interacts with a cellular
chemokine receptor to induce fusion
Other viruses are internalized by
endocytosis
In either case, the capsid, containing the
nucleic acid and viral enzymes, is dumped
into the cytoplasm
14.2 Interactions of Animal Viruses
and Their Hosts
Step 3: Targeting to the site of viral replication
Most DNA viruses replicate in the nucleus
Most RNA viruses replicate in the cytoplasm
Some viruses integrate their dsDNA into the
host cell’s genome (i.e., chromosomes)
Some viruses copy their RNA into dsDNA,
which is then integrated into the host cell’s
genome
14.2 Interactions of Animal Viruses
and Their Hosts
Step 4: Uncoating
The capsid is composed of protein
subunits
The nucleic acid dissociates from the
subunits
This causes the capsid to disintegrate,
liberating the nucleic acid
14.2 Interactions of Animal Viruses
and Their Hosts
Step 5: Nucleic acid replication and protein
synthesis
RNA viruses
Some RNA virus genomes act as a mRNA (”plus-strand”
viruses)
All others (minus-strand viruses) possess a prepackaged,
virus-encoded RNA-dependent RNA polymerase
DNA viruses encode RNA polymerases
Many viruses have polycistronic mRNAs
Viral polypeptides are synthesized by the cell’s
translational machinery
14.2 Interactions of Animal Viruses
and Their Hosts
Step 6: Maturation
Cleavage of polycistronic polypeptides into
subunits
HIV gp160 polypeptide is cleaved into its
gp120 and gp41 mature polypeptides
This step is inhibited by the HIV
protease inhibitors taken by HIV+
patients
Nucleic acids and capsid proteins
spontaneously polymerize into
nucleocapsid
14.2 Interactions of Animal Viruses
and Their Hosts
Step 7: Release from cells
Some viruses rely upon cell lysis for release into
the extracellular environment
Other viruses rely upon budding, whereby they
exit from the cell, taking part of its membrane
(viral envelope)
Budding occurs at the plasma membrane, ER or
Golgi, depending on the viral species
If the rate of budding exceeds the rate of
membrane synthesis, then the cell will die
14.2 Interactions of Animal Viruses
and Their Hosts
Step 8: Shedding from the host
Viruses must leave the infected host to
infect other hosts
Shedding can be a minor event (such as
cold viruses) or a catastrophic event
(such as hemorrhagic fever viruses)
Step 9: Transmission to other hosts
Transmission routes usually reflect the
sites of infection for viruses (e.g.,
respiratory, GI, STD)
14.2 Interactions of Animal Viruses
and Their Hosts
Persistent infections
Latent - periods of inactivation and activation
(e.g., herpesviruses); usually limited pathology
Chronic - infectious virus can be detected for
years or decades with little discernible
pathology, but can eventually lead to disease
(e.g., hepatitis B and C viruses)
Slow infections - short period of acute infection
(weeks) followed by the apparent
disappearance of virus for months or years,
with pathology ensuing (e.g., HIV)
14.3 Viruses and Human Tumors
Tumor viruses drive cell proliferation
Several mechanisms account for this phenomenon
Viral oncogenes that stimulate cell proliferation
Viral DNA integrates adjacent to genes that drive
cell division
Expression of the viral genes leads to aberrant expression
of the cellular gene
Some viruses encode growth factors that
stimulate cellular proliferation
Epstein-Barr virus encodes viral interleukin-10 that causes
B cell proliferation, leading to Burkitt’s lymphoma
14.4 Viral Genetic Alterations
Segmented viruses contain multiple genetic
elements that encode different genes
Influenza viruses are the best characterized of
segmented viruses
The gene sequences of these segments within the
same species can vary, thus provide genetic
diversity
Coinfection of a cell with two or more different
strains of a virus, such as influenza A viruses, can
lead to the emergence of reassortant viruses that
have distinct characteristics
The process is termed reassortment
14.4 Viral Genetic Alterations
Influenza A viruses have 8 gene segments that encode 10
polypeptides
Segment 1 (2,341 nt): PB2
Segment 2 (2,341 nt): PB1
Segment 3 (2,233 nt): PA
Segment 4 (1,778 nt): HA (hemagglutinin) - 16 known subtypes
Segment 5 (1,565 nt): NP
Segment 6 (1,413 nt): NA (neuraminidase) - 9 known subtypes
Segment 7 (1,027 nt): M1, M2
Segment 8 (890 nt): NS1, NS2
The H5N1 influenza virus has subtype 5 HA segment and subtype 1 NA segment
14.5 Methods Used to Study Viruses
Cultivation of host cells
Embryonated chicken eggs
Must be susceptible to the virus
Two principal targets
Chorioallantoic fluid (CAF)
Embryo
14.5 Methods Used to Study Viruses
Cell culture
Cells must be susceptible to virus
Cells are grown attached to flasks in a monolayer
Cells are inoculated with virus
Within days, cytopathic effect (CPE) can be seen
Prions
14.7 Other Infectious Agents
Proteinaceous infectious particle
Cause spongiform encephalopathies
Characteristics
They contain no nucleic acids
They are a normal cellular protein (PrPc) that has misfolded
into a pathogenic protein
The prion protein “replicates” itself by causing copies of the
normal protein to misfold into the prion protein
Diseases
Creutzfeldt-Jakob (New Variant CJ from “mad” cows)
Kuru (religious consumption of brains from deceased)
Chronic wasting disease (elk, deer, moose)